Southwest Association for Education in Biomedical Research - SwAEBR

Research Focus 2002:

The Southwest Association for Education in Biomedical Research members are continually furthering research. This section will be to highlight ongoing research.

Genetic Cause of Heart Failure

Ovary transplants could help save rare species following the successful transplant of mouse ovaries into rats. Researchers grafted ovarian tissue from mice onto the kidneys of rats. Three weeks later mature eggs were collected and fertilised with mouse sperm. The resulting embryos were implanted into surrogate mother mice, and one in 10 resulted in live pups. Grafting ovarian tissue collected from living or recently dead animals may allow researchers to propagate rare and endangered species. Researchers are now applying the technique to the endangered northern hairy-nosed wombat. - Science, 27 September 2002

Ecstasy and Brain Damage
Just a couple of Ecstasy tablets can cause long-lasting damage to the brain, a study on squirrel monkeys has suggested. The drug, which is popular with clubbers, may also trigger Parkinson's disease later in life. Researchers have found that Ecstasy causes extensive damage to key brain cells, called dopamine neurons. Dopamine helps to control movement, emotional and cognitive responses and the ability to feel pleasure. However, a substantial loss of dopamine can cause Parkinson's. The researchers warned that people should be aware that the use of Ecstasy in doses similar to those used in recreational settings can damage brain cells, and this damage can have serious effects.  - Science, 27 September 2002

Gene Implicated in Oxidative Stress
Oxidative stress is implicated in a fast-growing list of human conditions, from the superficial (eg wrinkled skin) to the deadly: diseases such as cancer, heart disease and neurodegenerative disorders including motor neuron disease and Alzheimer's disease. Researchers have now located a gene in mice that protects certain brain and retinal cells from oxidative stress, and prevents neurodegeneration.  Many normal metabolic functions produce free radicals - highly unstable forms of oxygen, which in excess cause oxidative stress leading to cell damage. The research team discovered that mice from a strain called harlequin have a mutation in a gene called Aif, resulting in severe reduction in production of the AIF protein, which serves as a scavenger of free radicals in certain brain and retinal nerve cells. Because harlequin mice have much lower levels of AIF, nerve cells in these mice suffer oxidative stress and die. The harlequin mouse will thus aid the study of the role of oxidative stress in the death of nerve cells. - Nature, 26 September 2002

Gene Helps Nerve Cells Survive
Why do some nerve cells survive and regrow after injury while others shrink away and die? A new discovery shows that the expression of a particular gene may be responsible for protecting them from death. The results could lead the way for new treatments for a variety of neurological diseases.   Turning on a gene named Hsp27 could potentially rescue nerve cells in patients with neurodegenerative conditions such as motor neuron disease. The scientists found that, in the laboratory dish and in rats, young sensory and motor nerve cells die after injury because the heat shock protein 27 gene (Hsp27) is not turned on in these cells. In adult cells however, the gene is expressed. The protein that is produced protects these mature nerve cells from death following an injury. If the Hsp27 gene is delivered to young nerve cells using gene therapy, the cells are able to survive injury just as well as older nerve cells. Equally, if the gene is switched off in adults, those cells will die. -
Neuron, 26 September 2002

Risk Factor for Colon Cancer
Studies in mice and humans have revealed that carriers of the rare disease, Bloom syndrome, are at increased risk for developing colorectal cancer. In Bloom syndrome, people who have two defective copies of the BLM gene are generally of short stature and have a variety of physical defects and a predisposition to developing many types of cancer. Bloom syndrome occurs in all ethnic populations, but it is more common in Jewish people of European descent (Ashkenazi Jews). The new research shows that even carriers of the syndrome, who have just one defective gene and show no symptoms of the syndrome itself, are at increased risk of colorectal cancer.   The BLM protein plays a role in helping ensure that chromosomes are copied properly during cell division. When the BLM protein is defective or missing, cells are more likely to acquire or keep DNA-copying errors that result in mutation.  - Science, 20 September 2002

Regulating Heart Growth
Researchers have discovered a protein that regulates growth and development of the heart from its foetal stage to adulthood. The protein, named Homeodomain-Only Protein (HOP) by the researchers, is active in controlling heart growth at various stages of development in mice. After they identified HOP, they bred mice that were genetically unable to produce the protein, with dramatic results: they either died as embryos because their hearts didn't grow, or they survived to adulthood with too many cardiac muscle cells. Understanding the mechanisms that regulate growth of heart cells has important implications for eventual therapies directed toward repairing the damaged heart. HOP is likely to be just one important component that regulates heart growth and researchers need to find out how HOP is regulated in turn by other signals and proteins. -
Cell, 20 September 2002

Regenerating Muscle
Several forms of muscular dystrophy are caused by mutations that disrupt the dystrophin-glycoprotein complex, an assembly of muscle proteins. Dystroglycan is protein that is a major component of this complex. But when scientists removed this protein from skeletal muscles of mice, they were only mildly affected by muscular dystrophy. They found that so-called satellite cells stepped into the breach to produce dystroglycan. This finding offers hope that the progression of this and other muscle wasting disorders can be slowed by treatments that aim to keep muscles regenerating themselves.  - Cell, 6 September 2002

Gene Therapy Sets the Pace
Researchers have used gene therapy to fix the heart's pacemaker. If the treatment, carried out in guinea pigs, could be extended to humans, biological pacemakers might offer a cheaper and safer alternative to electronic implants.  The added gene changes the flow of chemicals into and out of heart cells. This creates an electrical charge, and turns ordinary cells into pacemakers. Pacemaker cells are a bit like nerve cells, providing an electrical jolt that starts the heartbeat and controls its rhythm. In the embryonic heart, every cell has pacemaking power. But in adults this power is suppressed in all but a small patch of cells where the heartbeat begins. Gene therapy was used to block this suppression in guinea pigs. - Nature, 12 September 2002

New Class of Tumor Suppressor
A new and unusual type of natural tumor suppressor protein has been discovered in mice. Researchers developed mice lacking the gene that produces this protein, called Lkb1. This gene is mutated in patients with Peutz-Jeghers Syndrome, a rare genetic disease resulting in many painful bleeding polyps in the gut and susceptibility to cancer. Lkb1 seems to have some cancer-causing, and some cancer-preventing, activity. Lkb1 deficiency somehow promotes perpetual cell growth but prevents cells transforming into cancers. This evidence places the gene in a distinct class of tumor suppressors.  - Nature, 12 September 2002

Wired for Movement
Scientists have identified a molecule that helps to wire up the nerve circuitry that controls muscle movement. The signaling protein named WNT-3 directs specific nerve cells during embryonic development to make the correct connections in the spine, forming a pathway that controls muscles. Understanding the complex web of instructions that directs this intricate process may have important implications for nerve regeneration following spinal injury.  Using embryonic mice, the scientists found that motor nerves in the spinal cord produce WNT-3 only at a crucial stage when sensory nerves come close to them. Sensory nerve cells carry information about muscle tension and body position to motor nerve cells in the spinal cord to control muscle contraction. During development of the brain and spinal cord a hundred million nerve cells are looking for partners to make connections with. It appears that motor nerves release the WNT-3 protein to guide sensory nerves to make connections with them.  - Neuron, 12 September 2002

Mast Cells Implicated in Arthritis
Mast cells are best known for releasing the allergy compound histamine, which induces running eyes and noses in hay fever, for instance. Now rheumatologists have found the cells embroiled in inflammatory arthritis: mast cells in mice act as a bridge linking self-attacking antibodies and the inflammation that swells joints.  Mast cell-deficient mice were resistant to a form of arthritis, and putting the mast cells back into these animals inflamed their joints, further implicating the cells directly in the disease. - Science, 6 September 2002

New Blood Vessels in Newborns
Newborn animals grow rapidly, and they must develop new blood vessels fast enough to keep pace with that growth. Researchers have found that a kind of immature cell that develops in the bone marrow and circulates in the blood contributes to the growth of new blood vessels in newborn mice.  The researchers also found that a substance produced by the body known as vascular endothelial growth factor (VEGF) causes the immature cells to form new blood vessels at a faster rate. This finding has important implications for tumor biology, gene therapy and the treatment of various congenital disorders.  - Proceedings of the National Academy of Sciences, 3 September 2002

Proteins Play Key Role in Aneurysms
A new discovery by a team of researchers using mice could lead to a drug treatment, instead of surgery, for aortic aneurysms. An aneurysm is a bulge in the wall of a blood vessel. It occurs most commonly when the wall of the aorta (the main blood vessel in the heart that travels to the legs and abdomen) becomes weakened. The vessel can get as big as a grapefruit before it ruptures, causing internal bleeding. About 16,000 people a year who experience ruptured aortic aneurysms die. Most people are unaware they have an aneurysm since normally there aren't any symptoms until rupture occurs.  Studying genetically modified mice, researchers showed that interaction between two enzymes called matrix metalloproteinases plays an important role in the formation of abdominal aortic aneurysms. A common antibiotic called doxycycline prevented aneurysms from enlarging in mice.  - Journal of Clinical Investigations, 1 September 2002

Sugar Therapy Could Prevent Kidney Damage
Targeting sugars that occur naturally in the body could protect the kidneys or other organs from damage associated with disease or injury, according to a study using genetically modified mice. It showed that knocking out the normal function of certain enzymes could protect the kidney from damage and inflammation following blood flow blockage. Such damage affects patients with conditions such as diabetes and acute renal failure, and can destroy donated kidneys. The findings also have implications for research into conditions like heart attacks and strokes, which have similar blood flow blockages.  The enzymes in question are called fucosyltransferases. During injury repair, they add the sugar fucose to the proteins that allow white blood cells to bind to the sites of damage. This causes inflammation and additional damage. Mice deficient in fucosyltransferase enzymes were protected against kidney dysfunction and damage after injury, and had a reduced number of white blood cells at the injury site, compared to normal mice.  - Journal of Immunology, 1 September 2002

Promise of Anti-angiogensis
For nearly five years, doctors have noted promising cancer-slowing results from early clinical trials of a drug that lowers the level of copper in cancer patients' blood. Now, new research results from mice have told them exactly how that experimental drug works, and showed them its cancer-fighting potential on a cellular level. The findings have implications for the approach to cancer treatment known as anti-angiogenesis.
The drug - tetrathiomolybdate, or TM - keeps tumor cells from sending signals that spur the formation of new blood vessels. The studies in mice showed that by keeping copper low and blocking a key signaling pathway, TM blocks angiogenesis, or blood-vessel creation. Angiogenesis is thought to be a common denominator for many kinds of cancer, allowing tumors to grow locally and to spread to the rest of the body. TM suppressed the growth of tumors in mice implanted with cells from an aggressive form of human breast cancer and prevented the formation of tumors in mice specially bred to develop breast cancer.  - Cancer Research, 1 September 2002

Barrier to Better Hepatitis A Vaccines
Researchers have located the genes that make hepatitis A (HAV) infectious. They also discovered that deliberately weakened HAV, when injected into monkeys, was able to quickly revert to its natural infectious form. This means it could be difficult to create an improved vaccine against HAV.  As sanitation improves in developing countries, there will be an increased need for inexpensive and easy-to-administer vaccines to prevent hepatitis A, which is transmitted through contaminated food and water. Almost all people in developing countries become infected with HAV during childhood and thereafter are immune to HAV. But improvements to water quality and sanitation mean that naturally acquired immunity may not occur as often.  People who become infected with HAV for the first time later in life are more likely to suffer serious illness and severe liver damage. While there is a vaccine made from killed HAV, it has to be administered in multiple booster shots. The expense and inconvenience of that vaccine restricts its use in developing countries.  - Journal of Virology, September 2002

Vaccine Prevents Stroke
A vaccine that interferes with inflammation inside blood vessels greatly reduces the frequency and severity of strokes in rats, according to a new study. If the vaccine works in humans, it could prevent many strokes.  In the study, researchers used a nasal spray to deliver a protein that, under normal circumstances, contributes to inflammation of the cells lining the inner walls of blood vessels. Exposing rats to this substance, called E-selectin, programs blood cells called lymphocytes to monitor the blood vessel lining for the inflammatory protein. When these lymphocytes detect E-selectin, they produce substances that suppress inflammation.  The vaccine is the first treatment to target inflammation in blood vessels as a possible means of preventing stroke. The researchers are now planning a small human trial to test the effects of human and bovine E-selectin vaccines in people at high risk for stroke. The bovine E-selectin will be tested in addition to the human protein because there is a chance it may produce a stronger response. - Stroke, September 2002

New Neurons, New Therapies
Insights into how brain cells respond to injury could lead to new ways of treating stroke and dementia due to cancer radiation. Using rats, scientists showed that a damaged area in the brain - akin to human stroke - is infiltrated by new nerve cells. It appears that new nerve cells are produced in a different area of the brain called the subventricular zone and travel to the site of injury. Once there, the cells take on the characteristics of the cells that were destroyed. The problem is that only 0.2% of the damaged nerve cells are replaced. However, finding a way of augmenting this natural re-growth may offer new therapies.   Other scientists have discovered why patients who undergo radiation therapy for brain, head or neck cancer suffer from some mental decline. Using rats, they found that radiation exposure drastically reduced the regenerative abilities of nerve cells in the hippocampus - a brain region involved in learning, memory and spatial awareness. Scientists believe that radiation affects the stem cells that give rise to these new nerve cells. Future treatment should therefore aim to protect, or replace, these stem cells during radiation treatment for such cancers.  - Nature Medicine, September 2002

New Ways to Treat Eye Disease
Using mice, a team of scientists has discovered that certain stem cells taken from the bone marrow may be able to treat eye diseases such as diabetic retinopathy and the deterioration of vision that is associated with old age. The findings also suggest that genetically modified stem cells could be used for local delivery of eye treatments, representing a new way of treating eye diseases. Diabetic retinopathy is a leading cause of blindness in the developed world, and almost all people who have had diabetes for more than 30 years will show signs of poor eyesight. Age-related macular degeneration is a common cause of vision loss among people over the age of 60. Both conditions are caused by damage to blood vessels in the retina.   Using mice, the scientists found that when particular cells, taken from mouse bone marrow, were injected into the eye, they attached to cells in the retina called astrocytes. Once there, the stem cells incorporated themselves into the existing blood vessel structure and formed new blood vessels. If genetically modified before being injected into mice eyes, they also stopped the proliferation of unwanted blood vessels. - Nature Medicine, September 2002

Human Antibodies from Cloned Cattle
So-called polyclonal antibodies - natural components of the human immune system - show promise for curing numerous ailments including cancers and infectious diseases. But the only source of these antibodies is human donors, so the supply is very limited. Moreover, it would not be ethical to immunize patients with dangerous antigens to produce the desired antibodies.  Scientists have now cloned calves that produce human antibodies in their blood. To achieve this, the scientists supplemented the animals' normal genetic material with a synthetic human chromosome carrying the genes for the two proteins needed to form human antibodies. Although human antibodies have been produced before in mice, cows could manufacture much larger amounts.  Several major hurdles must still be overcome before human antibodies from cows could reach the clinic. For example, scientists will need to purify the antibodies and ensure that they are free of viruses.  - Nature Biotechnology, September 2002

Getting Under the Skin
Between unrelated individuals, tissue transplants such as skin, which do not have their own blood vessels, do not 'take' because T cells in the immune system attack the tissue. Using mice, researchers found that donor skin was rejected not by direct attack on the grafted skin cells, but rather by attacking the newly formed blood vessels that grew from the host into the graft. Organ grafts such as hearts were not rejected, however, presumably because these grafts used their own blood vessels. These results may explain why skin is so difficult to transplant and may be applicable to the treatment of other diseases, such as cancers, that rely on fresh blood vessels.  - Nature Immunology, September 2002

Lungs May Become Drug Factory
Gene therapy that converts a patient's lungs into a living, breathing medicine factory could one day eliminate regular drug doses for diabetics and hemophiliacs, new studies suggest. Patients could inhale therapeutic genes in aerosol sprays. Gene therapy adds working genes to tissues that have defective ones, but most research has focused on supplying lung genes to sick lungs and muscle genes to ailing muscles.
In a new twist, researchers have added to the lungs of mice a gene that encodes the protein missing from some hemophiliacs' blood. They used a new strain of adeno-associated virus that efficiently injects genes into lung cells. For months the animals' airways continued to produce the protein, called factor IX, at levels suitable for treatment. The team also demonstrated the technique's potential to supply erythropoietin, a substance that stimulates the production of red blood cells and is used to treat chronic kidney failure. Other researchers are turning muscle and liver into drug factories and some researchers have proposed co-opting the gut in a similar way.  - Journal of Clinical Investigation, 15 August 2002

Deaf Mouse Clue to Human Hearing Loss
Scientists have discovered defects in a gene in mice that have led to the identification of similar genetic defects in people with hearing loss. The findings may eventually lead to a screening test and therapy for families affected by one type of inherited hearing loss. The discoveries also bring scientists closer to understanding the intricate choreography of genes and proteins involved in the normal development of human hearing - and the tiny missteps that can destroy hearing even before a baby is born.  The discovery of the human deafness gene, called TMIE, relied on the discovery of a mouse gene, Tmie. Once scientists found the gene, and the mutations that caused deafness in two strains of mice, they explored how those mutations affect the structure and function of the inner ear, leading to deafness. The mutations appear to alter the tiny hair-like stereocilia that coat the hair cells of the inner ear and are crucial to hearing.  - Human Molecular Genetics, August 2002, American Journal of Human Genetics, September 2002

Glowing with Health
Using a mouse that literally glows with health-protecting molecules, researchers have rewritten part of the textbook about how the immune system knows when to fight germs. Time-lapse video showed how pieces of captured germs work their way to the surface of dendritic cells. Dendritic cells are sentries that alert other immune cells about invading germs. Inside a dendritic cell, the video showed that molecules with the job of carrying germ fragments shoot toward other immune system cells, T cells, along long tubules. The fragments, called antigens, alert T cells to kill the invading germs.  These are the first studies using cells from a new genetically engineered mouse, whose antigen-carrying molecules have been genetically tagged with green fluorescent protein. It is thought that the dialogue between the dendritic cell and the T cell improves the efficiency of the immune response to invading germs, and it is becoming clear that dendritic ecells are as important as T cells in initiating or suppressing an immune response.  - Nature, 29 August 2002

Cell Therapy May Aid Stroke Victims
Transplants of versatile human bone marrow cells have improved recovery from stroke in rats. This therapy shows promise in treating stroke, Parkinson's disease, spinal cord injury and traumatic brain injury.  For the study, bone marrow cells were taken from three healthy human donors. Strokes were then induced in the rats and they were given the cells intravenously one day after the stroke. Other groups served as controls. The rats were tested on their abilities and on their reflexes before the stroke and at one day, seven days and 14 days after the stroke. Two weeks after the stroke, the treated rats completed tests 60% faster than the non-treated rats. A detailed examination showed that the treated rats had a 30% improvement in overall neurological score. Trials on humans will be the next step. - Neurology, 27 August 2002

Gene Breakthrough on Abnormal Heart Growth
Using genetically engineered mice, researchers have identified a gene - HDAC9 - they believe could predict risk for developing enlarged hearts and lead to treatments to control life-threatening heart growth. Doctors have long understood that the heart becomes enlarged - a condition called cardiac hypertrophy - when it responds to stresses, including irregular heartbeats and high blood pressure. Enlarged hearts frequently become dilated and work less efficiently. The excess muscle can also disrupt the electrical signals that control heart rhythm. Cardiac hypertrophy can cause sudden death in young athletes, who may suffer cardiac arrest without ever knowing they had the condition.  The study showed that HDAC9 specifically restricts cardiac growth in response to stress, but it does not restrict normal cardiac growth during development or in response to exercise. In future it may be possible to identify people who don't yet have enlarged hearts but have mutations in that gene, and warn them of the risk. The knowledge that HDAC9 is a key regulator of heart growth could also lead to the development of new drug treatments. - Cell, 23 August 2002

Natural Born Killers Fight Anthrax
Researchers have developed a promising method for rapidly and effectively treating people infected with anthrax - including feared drug-resistant strains - and have proved its success in mice. The new research takes advantage of anthrax's number one natural enemy: bacteriophage, or "bacteria-eating" viruses. The technology also shows promise as an anthrax detection and decontamination tool.
Scientists focused on phage that specifically infect the biowarfare agent Bacillus anthracis - anthrax. They isolated the enzyme that allows these phage to rupture and escape from the anthrax bacterium and showed that drops of it can almost instantaneously destroy a test tube full of these deadly bugs. They tested the enzyme on mice infected with a close cousin of anthrax, called Bacillus cereus. Normally all mice die within four hours of being infected with this strain. But when the researchers injected a dose of the new enzyme 15 minutes after the mice were infected, three-quarters of them lived.  - Nature, 22 August 2002

Deviant Gene May Up West Nile Risk
A study in mice suggests that a flawed gene may be the reason the West Nile virus causes a severe, life-threatening illness in some while giving others only a relatively mild infection. Mice carrying the faulty gene were quickly killed by the West Nile virus, while mice with normal genes survived. If a similar gene variation is found in humans, it may lead to a new understanding of why only about one in five people infected with the virus develop a serious illness. It could also lead to a drug that would restore the missing protein and give patients protection against replication of the virus. - Proceedings of the National Academy of Sciences, 20 August 2002

Stem Cells Survive into Adulthood
Scientists know that stem cells exist in the adult central nervous system. New research using rats gives the first indication that they also remain in the peripheral nervous system - not only after birth, but also into adult life. The central and peripheral nervous systems develop from two different locations in the early embryo. Stem cells in one area create the central nervous system's brain and spinal cord. Stem cells from another area, called the neural crest, give rise to peripheral nerve cells and glial cells that control gut function, regulate the fight-or-flight response and make it possible for us to have a sense of touch. Glial cells are supportive cells for the nervous system. It isn't known what these neural crest stem cells are doing in the gut or whether they persist into adult life in humans, as they do in rats. Further research could lead to new ways of using stem cells to promote nervous system repair after injury or disease.  - Neuron, 15 August 2002

Working Womb Transplants
Scientists have managed to produce pregnancies - and healthy babies - in a womb transplanted into a mouse. This marks the first time a uterus from one animal has been transplanted into another and resulted in a successful pregnancy, but more evidence of success in other animals will be required before such an attempt can be justified in women.  Around 15% of all couples are infertile. Most causes can be treated by in vitro fertilisation (IVF) and sperm injection (ICSI). However, for women who have healthy ovaries, but have had a hysterectomy or uterus problems caused by injury or congenital conditions, a transplant is their only hope of carrying a child of their own. At the moment, they can choose IVF surrogacy, where their egg and their partner's sperm can be used, but the baby carried by another woman. Technically, this is straightforward but it may not always be suitable.  - Journal of Endocrinology, August 2002

How Herpes Tricks the Immune System
Herpes viruses enter the body and hide away in cells, often re-emerging later to cause illnesses such as shingles, genital herpes and cancer. How these viruses evade the immune system remains poorly understood, but researchers have discovered that a mouse herpes virus uses molecules called RCA that mimic a cell's own proteins to help thwart an immune attack. The findings also suggest that a branch of the immune system known as the complement system may play a more important role in controlling herpes virus infections than previously thought. Targeting RCA or manipulating the complement system may result in better treatments for herpes virus infections. - Immunity, August 2002

Malaria Vaccine Targets Toxin
Researchers have developed a novel approach to developing a vaccine against malaria. There is a long history of attempts to develop antimalarial vaccines, but with little success. All current malarial vaccines target proteins in the various life stages of the malarial parasite, Plasmodium falciparum. The new research using mice shows that a vaccine targeted at a toxin released by the parasite may be more effective. Mice inoculated with the toxin GPI were protected against many of the signs of malaria, and against death. The findings demonstrate the potential of synthetic GPI in anti-toxic vaccines, and suggest that GPI is responsible for some symptoms of malaria in humans. - Nature, 15 August 2002

Cross Species Testes Transplant
Researchers have produced sperm from pig and goat testes grafted onto mice. Future human-to-mouse grafts could help restore fertility to men who have undergone cancer therapy, and other interspecies grafts could help conserve endangered species.  Scientists have previously grafted testis tissue from one mouse to another - but previous grafts between mammalian species have not produced sperm. Now they have devised a technique to graft fragments of tissue from immature testes of newborn pigs or goats under the skin of mice whose immune systems were deficient. More than 60% of the grafts survived and produced working sperm. Unlike use of frozen sperm, grafting testis tissue from humans into a mouse and use of the resultant sperm for assisted fertilization provides a potentially endless supply of sperm. Testis tissue grafts could also contribute to conserving endangered species or valuable livestock by allowing sperm production from immature males. It could also be used as a method for studying the effects of toxins and male contraceptives on testis function. - Nature, 15 August 2002

Peptide Suppresses Multiple Sclerosis
A peptide that blocks interactions between cells in the immune system can inhibit and suppress a disease (EAE) in mice that mimics multiple sclerosis in humans. The finding suggests a possible new approach for treating this chronic human disease.  In mice, a single administration of the peptide suppressed the disease. The peptide is a specially engineered fragment of the CD28 molecule, that acts as signal in the immune system. The peptide fragment interferes with the interaction that prompts T cells to attack nerve cells in MS.  - Journal of Immunology, 15 August 2002

Synthetic Poliovirus Constructed
For the first time, scientists have used the genetic map of the poliovirus to construct a man-made version of the crippling virus. The synthetic virus was infectious to mice. The scientists say that this illustrates the potential for humans to manufacture viruses for use as bio-weapons: if viruses no longer found in nature can be reconstituted, then this has important implications once the poliovirus has been eradicated. - Science, 9 August 2002

Surprise, Surprise:  Epilepsy in Rats
Scientists interested in how and why nerve cells die in neurodegenerative diseases like motor neuron disease have produced rats with epilepsy, a disease characterized not by cell death, but by rapid and uncontrolled firing of brain cells.   Aware that extra amounts of the messenger called GABA can kill brain cells by over-stimulating them, the scientists blocked one of the messenger's main transporters in rats. But this didn't kill nerve cells; instead, the rats developed epilepsy. Epilepsy has long been tied to reduced levels of GABA, which dampens cells' likelihood of firing. However, the transporter molecule under study had never been linked to epilepsy in animals or people. Investigating further, the scientists discovered that the transporter imports glutamate molecules that are used by the cell to make new GABA molecules. The rats couldn't make new GABA, so their GABA levels dropped and epileptic symptoms developed.   Getting more glutamate into GABA-producing nerve cells may help calm the excessive electrical firing of brain cells.  - Journal of Neuroscience, 1 August 2002

Gene Therapy Boosts Cancer Chemotherapy
Researchers have found a way to combine cancer chemotherapy with gene therapy to disrupt the growth of blood vessels to a tumour. The combination, tested in mice, is far more effective than standard chemotherapy and has no additional side effects. This new approach builds on a similar system, now in human trials, that combines gene therapy with radiation therapy.   The therapy inserts the gene for tumour necrosis factor (TNF) into cells within a tumour. TNF is a potent biological substance that can kill cancer cells directly and disrupt their blood supply, but it can be very toxic to healthy cells. The researchers originally altered the TNF gene so that it could be turned on by radiation therapy. Now they have produced a version of the gene that can be activated by the common anti-cancer drug cisplatin. Mice treated with both the gene injections and cisplatin had high concentrations of TNF within tumours, but nowhere else. The combined therapy was far more effective than either cisplatin or TNF-gene injections alone, resulting in significant regression with no additional toxicity. - Journal of Clinical Investigation, 1 August 2002

Drug Slows Breast, Prostate Cancers
In recent years, discoveries in animals have led to the development of new drugs designed to target and attack cancer cells, leaving healthy ones intact. One key weapon in this arsenal of new therapies is called Herceptin, a drug that is currently used to treat breast cancer and works by targeting a specific protein that controls cell growth, called HER-2/neu. But despite the drug's effectiveness, tumors shrink only in breast cancer patients whose cancer cells express an over-abundance of HER-2/neu.  Now, using mice, researchers have found that a potent experimental drug called 2C4 slows tumor growth in both breast and prostate cancers even when only small amounts of HER-2/neu are expressed. The 2C4 drug is a monoclonal antibody, or molecule that enlists the body's immune system to attack foreign invaders, such as viruses or bacteria. It not only targeted HER-2/neu, but disrupted cell signaling among the entire HER family of proteins. As a result of these mouse studies, clinical trials are currently underway to test the safety and effectiveness of 2C4 in patients with breast and prostate cancer, as well as other solid tumors. - Cancer Cell, August 2002

What Goes Wrong in Huntington's
Huntington's disease, a devastating neurodegenerative disorder, is caused by a mutation that inserts a repeating sequence into the huntingtin gene. Studies on mice and patients have shown that the mutant protein may damage brain cells by interfering with their mitochondria, the energy producing mechanism of cells. This may lead to treatments that would slow the progression of Huntington's disease, as well as other diseases caused by mutations that insert repeated sequences into genes.  The researchers isolated mitochondria from patients with Huntington's disease or from mice that produced a mutant form of huntingtin. Both types of mitochondria were defective, responding to unusually small amounts of calcium. These defects were apparent well before mice start to develop the movement disorders and neurodegeneration characteristic of Huntington's disease. The abnormalities observed in mitochondria from patients or mutant mice were reproduced by applying proteins containing the mutant repeat directly to mitochondria from normal subjects. Future studies will need to identify how the abnormal regions of huntingtin interfere with mitochondrial function.  - Nature Neuroscience, August 2002

Cloned Cows Produce Human Antibodies
Cloned cows producing human antibodies could soon be drafted into the battle against a wide variety of microbes, including anthrax and smallpox.  Scientists used artificial chromosomes and cloning technology to create cattle that contained a full suite of functional human antibody genes. However before these antibodies can be used in patients, the researchers need to knock out the cows' own antibody genes. This would make it possible to harvest pure human antibodies from the animals, and should happen within two years.   The need for human polyclonal antibodies is growing. They are currently used to treat patients with hereditary immune deficiencies and certain viral infections, as well as holding great potential as tools to fight biological warfare agents. A human-mouse antibody gene swap has been accomplished in mice, but rodents cannot produce large quantities of antibodies. At present, human volunteers are the only source of these antibodies. This means that both supply and applications are limited, because you can't give a human volunteer booster shots of anthrax proteins to develop a potent antibody response. - Nature Biotechnology, August 2002

Cloned Transgenic Fish
Scientists have developed a cloning technology that will allow them to study how alterations in specific fish genes affect development and behavior. Zebrafish are popular with geneticists interested in studying vertebrate development because they are small, easy to maintain, and grow and reproduce very quickly. What's more, the transparent embryos of zebrafish are ideal for visualizing changes during development.
Researchers grew zebrafish cells on a plate for three months, transferred the nuclei of these cells into recipient zebrafish eggs lacking a nucleus, and produced live transgenic offspring. Until now, nobody had been able to clone zebrafish from long-term cell cultures, which allows the introduction of specific genetic changes. To achieve this, the researchers introduced a foreign gene before the cloning procedure, and produced 11 fertile adult transgenic zebrafish expressing the foreign protein. Although the rate of transgenic clones reaching adulthood was fairly low (2% of all experiments), and 80% of nuclear transfer attempts did not yield developing embryos, all of the successful transplants expressed the foreign protein.  - Nature Biotechnology, August 2002

New Brain Cells, New Therapies
Insights into how brain cells respond to injury could lead to new ways of treating stroke and dementia due to cancer radiation. Using rats, researchers showed that an area of brain damage akin to human stroke was infiltrated by new nerve cells. It appears that these cells are produced in a different area of the brain and travel to the site of injury. Once there, they take on the characteristics of the cells that were destroyed. The problem is that only 0.2% of the damaged cells are replaced. However, finding a way of augmenting this re-growth may offer new therapies.  In separate research, scientists have discovered why radiation therapy for brain, head and neck cancers can affect patients' mental abilities. Using rats, they found that radiation exposure drastically reduced the regenerative abilities of nerve cells in the hippocampus - a brain region involved in learning, memory and spatial awareness. They believe that radiation affects the stem cells that give rise to new hippocampal nerve cells. Future treatment should therefore aim to protect, or replace, these stem cells.  - Nature Medicine, August 2002

Early Eggs Make Mice
Normally it takes an adult female mouse to produce a fully functioning mouse egg. Now researchers have removed immature egg cells from foetal mice and completely matured them in the test tube, with a success rate of over 90%. They guided the immature cells through complex chemical and genetic stages while keeping them in culture for 28 days. They then fertilised the eggs in the test tube and transferred them to surrogate mothers, who produced healthy, fertile offspring.   The techniques will give researchers a window on egg development, and may help us understand infertility and birth defects. If the methods can be used in humans - which is still some way off - they could save the fertility of women undergoing chemotherapy or radiotherapy, by removing an ovary before treatment. And being able to rescue and develop the huge numbers of immature egg cells that normally go to waste may eventually help efforts to breed endangered species.  - Nature, 1 August 2002

Measles Immunity on a Plate
Lettuce might replace booster shots in the next generation of vaccines. Researchers have increased the immunity of mice to measles by feeding them a booster vaccine derived from plants. The study is a step towards an edible measles vaccine for developing countries that would not require refrigeration or skilled medical personnel to deliver jabs. Measles kills an estimated 800,000 people a year, predominantly African infants.  Researchers injected mice with a DNA measles vaccine. After the first injection the researchers fed the animals tobacco plant extracts containing the same viral protein. The extracts came from plants that had been genetically modified to express the measles protein inside their cells. The mice fed the extracts from the modified plants had much higher levels of antibodies against measles than animals fed extracts from ordinary plants. The combination of DNA and oral vaccine raised antibody levels beyond what is considered protective against measles in humans.  To move towards a truly edible vaccine, the team has produced the measles protein in lettuce and in rice, which could be ground into cereal for infants. Next they will test their vaccination strategy in monkeys. - Journal of Virology, August 2002

Gene Involved in Autoimmune Disease
Researchers have identified a gene in mice that appears to be a critical factor in autoimmune diseases. Autoimmune diseases occur when an individual's immune system launches attacks on its own tissue confusing itself as a foreign invader, and include various disorders such as multiple sclerosis and rheumatoid arthritis.  The research could provide a unique view of the molecular defects underlying autoimmune disease. Using molecular techniques to study the genetic material from autoimmune disease-susceptible mice, scientists were able to identify a region of the mouse chromosome, and subsequently a gene, that correlates with autoimmune disease. The gene produces a protein that responds to histamine, a signaling molecule involved in immune responses.  - Science, 26 July 2002

Defect Causes Rare Muscular Dystrophies
Subtle defects in the processing of a single protein that protect muscle cells from damage can lead to several devastating forms of muscular dystrophy, according to studies involving mice and patients with these diseases. Scientists found that enzymes which process the structural protein dystroglycan are the underlying cause of several rare forms of muscular dystrophy that affect muscles and cause additional developmental brain abnormalities including mental retardation.   Two studies demonstrated that dystroglycan is defective in muscle-eye-brain disease and Fukuyama congenital muscular dystrophy. Separate genes had already been identified as defective in these syndromes, but researchers have not understood the underlying mechanism until now. The new findings will help doctors to provide accurate diagnosis and genetic counseling to patients and their families. In the longer term, knowing the underlying cause of the muscular dystrophies will help doctors tailor treatments.  - Nature, 25 July 2002

Mice Shed Light on DNA Repair
An enzyme in mice called MBD4 appears to help fix naturally-occurring DNA mutations, according to a new study. This is the first proof that there is a 'repair kit' for damage caused by DNA methylation, a cellular process that shuts genes down by marking them with chemical switches called methyl groups. The methyl groups work well to silence genes, but in doing so they greatly increase the chances of mutation. By using mice lacking the MBD4 gene, researchers showed that one in three mutations that cause human disease could be attributed to methyl groups on our genes. No amount of care in avoiding harmful agents in food or air can escape this problem.  The human gene that produces the human equivalent of MBD4 is known to be mutated in certain human cancers. However, there are no immediate implications for cancer therapy, because making this enzyme more efficient at repair would take a very long time.  - Science, 19 July 2002

Modified Mice Clue to Autism-like Disorder
Scientists have developed an animal model for Rett syndrome, a disabling developmental disorder that strikes mostly young girls. By tweaking a certain mouse gene, MECP2, researchers were able to raise rodents that exhibited many of the symptoms seen in children who have Rett syndrome, such as tremors, seizures, anxiety and hand-wringing. Approximately 1 in 20,000 children are born with the syndrome. Like children with Rett syndrome, the mice appeared to be developing normally at first. But after two to three months, they began to display many of the neurological features of the syndrome, which is a type of mental retardation sharing many similarities with autism.   Having a mouse that shows Rett syndrome symptoms should make finding treatments for the disease easier. The mouse will also allow researchers to study what goes wrong in people born with the syndrome, and to learn whether it can be reversed.  - Neuron, 18 July 2002

Extending Lives with Prion Disease
Scientists have lengthened the life of mice with scrapie, a prion illness similar to mad cow disease (BSE/CJD), with a compound that could provide a new approach to treating affected humans. They injected the rodents with a product designed to stimulate an immune response. Mice given the experimental treatment lived 38% longer than those who received a placebo.   The scientists are not sure how the compounds (CpG oligodeoxynucleotides) worked, but they are safe for humans. CpG molecules mimic some properties of bacterial DNA and activate immune responses. - Science, 5 July 2002

Turn Back the Developmental Clock
A new study shows for the first time that a unique pattern of cellular activity found in early brain development also triggers repairs to damaged adult brains. The findings hold implications for treating brain damage caused by stroke and other disorders.   Researchers using rats showed how cells in stroke damaged brains become active to trigger sprouting of new connections into areas of the brain disconnected by the damage. Scientists and doctors had recognized this pattern of activity for many years after brain injury in humans, but its function remained unknown. A better understanding of how the brain recovers from injury will allow manipulation of the repair process and maximization of recovery from brain damage caused by stroke and other disorders.  - Journal of Neuroscience, 15 July 2002

Potential Liver Cancer Treatment
A team of researchers has identified and successfully tested in animals a potential new treatment for liver cancer, a disease for which there are few effective treatments. Most patients die within six months.  Only cancer cells, not healthy cells, were killed when the energy blocking compound, 3-bromopyruvate, was given to rabbits with liver tumors. It was dramatically less toxic than a currently used treatment for human liver cancer, called chemoembolisation, which delivers a dose of chemotherapy to the tumor and also blocks off the artery that feeds it. Before 3-bromopyruvate can be tested in humans, scientists would need to learn how normal cells protect themselves, whether the compound causes long-term damage to normal tissues, and how increasing the dose affects the animals. Secondary tumors that spread to the liver from elsewhere frequently hasten death from other, more prevalent types of cancer, such as skin, colon, breast and prostate cancers. If tests on such cancer cell types are promising, the compound might be useful for treating any tumor in the liver, not just those originating there.  - Cancer Research, 15 July 2002

Hitting Cells When They're Down
Scientists have suggested a new, potentially more effective way to tackle cancer - hit the immune system with cancer vaccines or cancer cells when it's down and it will bounce back harder than ever against those cancer cells. The new variation on 'immunotherapy' involves administering an injection of fresh immune cells to replace the ones that die immediately after chemotherapy or irradiation.   The studies in mice suggest that immunotherapy should be initiated immediately after chemotherapy or irradiation because the reduction in the body's T cells - a state called lymphopenia - is actually an advantage. The researchers were able to protect mice from tumor formation and existing tumors shrank.  - Journal of Clinical Investigation, 15 July 2002

On/Off Swith for Oncogenes
Among the many new strategies being developed for cancer therapy are drugs that inhibit the function of genes involved in promoting tumor growth - oncogenes. Such drugs might be toxic if used in the long term, yet they might be ineffective in the short term because of possible reactivation of the gene once treatment is stopped.   Scientists used mice to examine what happens to tumors induced by the MYC gene when it is briefly inactivated and subsequently reactivated. They were surprised to find that temporary inactivation of the gene leads to permanent loss of cancer producing cells. These results suggest that brief inactivation of an oncogene may permanently change the environment of a tumor cell so that it cannot revert to its original malignant behavior. - Science, 5 July 2002

Flicking the Genetic Switch
Genes that are inappropriately turned on play a critical role in triggering some diseases. Scientists have developed a gene-therapy technique to switch off genes in mice. The finding could potentially lead to ways of treating such diseases as cancer, hepatitis C and AIDS.   In plants and lower organisms such as flies or worms, researchers can experimentally switch off genes by inserting RNA. Initial attempts to use RNA inhibition in mice were unsuccessful, but now injection of DNA that produces a novel, hairpin-shaped, form of RNA has succeeded in halting hepatitis C infection in mice. The effect is long lasting, because even after the hairpin RNA breaks down, DNA remains in the cell and continues producing new RNA. The ultimate goal is to use this as a gene therapy to deactivate virus genes or genes involved in cancer.  - Nature, 4 July 2002

Gene Linked to Diabetes
A newly discovered gene plays a dramatic role in diabetes among rats, and is also present in nearly identical form in humans. For more than 20 years researchers have been studying a particular breed of rat, known as the BB rat, which naturally develops type 1 diabetes and dies unless given insulin. The researchers identified a novel gene, dubbed Ian5, with a mutation that results in the deletion of a protein that is found in, among other places, the thymus. Researchers hope that a better understanding of the gene and the function of the thymus could help find answers for diabetes.  - Genome Research, July 2002

Re-establishing the Connection
Human nerves grown as cells cloned from a tumor helped restore the function of injured spinal cords in rats. Transplants of these specially treated cells were used to patch a short circuit in the spinal cord of rats. The cells are safe, survive and can electrically reconnect the undamaged parts of the spinal cord.  A couple of the spinal cord-injured (SCI) rats could bear weight on their hind legs following transplantation with the experimental cells. However, the researchers emphasize that more studies are needed to determine if rats with reconnected spinal cords can walk again. They are hopeful that their work will ultimately lead to the first transplant of similar cells to treat spinal cord injury in humans.  - Journal of Neurosurgery: Spine, July 2002

Improving Bone Marrow Transplants
Scientists have uncovered a key mechanism that enables stem cells to exit the bone marrow into the blood circulation of healthy donors, as well as patients suffering from leukemia, other cancers and blood disorders. The findings, in immunodeficient mice, may lead to more efficient clinical stem cell transplants.   Bone marrow transplantation is a last-resort treatment that saves the lives of many patients with cancer and inherited blood disorders. In a transplantation, the patient's malignant or defective stem cells in the marrow are destroyed, and healthy stem cells must be encouraged to come out of the marrow into the bloodstream. Thus, scientists have been trying to find out what triggers stem cell mobilization. They discovered that degradation of SDF-1, a key protein in the bone marrow, is crucial for stem cell mobilization.
It is unclear whether the bacteria would be as infectious in humans as they were found to be in mice. - Nature Immunology, July 2002

Vaccine Tackles BSE-type Disease
Researchers have developed a vaccine that delays the onset of a mad-cow-like disease in mice. Though preliminary, the results could lead to vaccines against scrapie in sheep, BSE in cattle and variant Creutzfeldt-Jakob disease (vCJD) in humans.   These brain diseases, called transmissible spongiform encephalopathies, are thought to be caused by prions. These proteins become pathogenic when they change shape. Previous research has suggested that recombinant mouse prion - a bacteria-produced form of the normal protein - causes an immune response in mice that could block infection by the disease-causing mouse prion. However, these studies had only been performed in tissue culture cells or with mice that were genetically altered to produce abnormal immune responses.  Now, a team of researchers has shown for the first time that the recombinant mouse prion can work as a vaccine to postpone the appearance of prion disease in normal mice. - American Journal of Pathology, July 2002

Complex Gene-swapping Spawns Lymphoma
Researchers have identified how a form of lymphoma develops when large pieces of chromosomes swap locations. Their observations about how chromosome rearrangements, or translocations, cause pro-B cell lymphoma in mice offer a fresh perspective on how cancers arise from an increased "dosage" of specific genes or regions of the genome.  The discoveries in mice should lead to a better understanding of how deficiencies in DNA repair and in the DNA damage detection mechanism can produce tumor-causing changes. Such damage is seen in many human cancers. Although there have been theories about their origin, until now the mechanisms by which they might occur have remained unclear.  - Cell, 28 June 2002

Compound May Help Brain After Stroke
Injections of a naturally-occurring compound can prompt the growth of new nerve fibers and restore some functions lost after a stroke, according to researchers who have tested the compound on rats. They found that injections of inosine, a natural chemical, caused the undamaged side of the brain to develop new nerve circuits that helped to restore function in rats.  - Proceedings of the National Academy of Sciences, 25 June 2002

ACE2 Sets Heart Beating
A recently discovered protein is important for heart function. The protein, called angiotensin-converting enzyme 2 (ACE2) is made in the heart and kidneys and seems to be involved in regulating blood pressure and heartbeat. Studying rats with high blood pressure, scientists pinpointed the location of the ace2 gene on the X chromosome of rats. These hypertensive rats had reduced levels of the enzyme. The researchers also deleted the gene in mice. These animals have normal blood pressure, but their hearts work poorly as they get older. Disrupting the equivalent gene in the fruitfly Drosophila is lethal, owing to defects in heart development. It's possible that some human heart disease is related to ACE2 malfunction, but how this might happen is as yet unknown.  - Nature, 20 June 2002

Keeping Hemoglobin in Balance
Researchers working with genetically modified mice have discovered a gene and its associated protein that may have major implications for red blood cell formation, specifically for hemoglobin, which carries oxygen in red blood cells. Understanding how this protein functions may eventually lead to novel treatments for the hemoglobin-related blood disease, thalassaemia.  Thalassaemia is the most common single-gene disease known. The most severe form of the disease, beta thalassaemia major, affects 300,000 patients worldwide. Thalassaemia results from an imbalance between two proteins in hemoglobin, called alpha and beta globin. An excess of either type of protein is toxic, causing thalassaemia symptoms including poor growth, fatigue, bone damage, or skin ulcers.  The newly found protein, alpha hemoglobin stabilizing protein (AHSP), binds to free alpha globin and stops it damaging red blood cells. The researchers genetically engineered mice to lack the gene that produces AHSP. These mice showed blood abnormalities similar to those found in thalassaemia.  If physicians can deliver AHSP or a similar agent to patients with thalassaemia, they may produce a new treatment for the disease. Severe cases are now treated with frequent blood transfusions that carry their own serious complications, such as excess iron.  - Nature, 13 June 2002

Regrowing Nerve Cells in Rats
Adding a particular molecule to damaged nerve cells helps them to regrow following injury, according to new research. A modified version of this technique may one day enable doctors to treat people who suffer from paralysis and other conditions following spinal cord injuries.
Researchers performed experiments on rats that enabled the rats to regrow the nerve cell structures that normally connect the cells to the spinal cord. The researchers gave the rats a cell signaling molecule called cyclic AMP (cAMP), which has been shown to help nerve cells regrow in test tubes, before injury to their spinal cords. Although mammals such as rats and humans are not usually able to repair those types of injuries, the structures connecting the nerve cells to the spinal cord grew back. The next step is to see whether administering cAMP after an injury can enable the nerve cells to regrow.  - Neuron, 13 June 2002

Insulin Produced in Liver-Cell Transfer
Researchers have shown that adult rat liver cells can differentiate into insulin-producing pancreatic cells, a development they are calling a breakthrough in diabetes research. Preliminary findings also indicate that when large numbers of the new pancreatic cells are injected into diabetic mice, they can reverse the animals' high blood-sugar levels and make them normal. Someday the liver could provide cells capable of producing insulin for patients with diabetes. That would be significant, as it is more invasive and dangerous to retrieve stem cells from the pancreas than from the liver.   Scientists isolated stem cells from adult rat liver and then placed them in a high-sugar solution. The cells began to make insulin, which is not something liver cells normally do. In a group of six diabetic mice, three were left untreated. But in the other group of three, one mouse was given a high number of insulin-producing cells, and its blood-sugar levels dropped to normal within 10 days. Another two mice received much smaller numbers of cells and remained diabetic. - Proceedings of the National Academy of Sciences, 11 June 2002

Researchers have demonstrated in mice that a new drug formed by linking a growth factor to a toxin will target and destroy the blood vessels supplying a malignant tumor. Tests of the compound called VEGF/rGel in mice showed it could selectively destroy blood vessels supplying human solid tumors without harming the blood vessels of normal tissue. This is like a 'Trojan horse' approach to kill the blood vessels that supply solid tumors. The vascular endothelial growth factor (VEGF) is a carrier to deliver a toxic agent selectively to the tumor's blood supply - in effect, starving the tumor. For the study, mice with human skin cancer or prostate cancer that received VEGF/rGel had reduced cancer growth compared with untreated mice, with no damage to organs. Tumor suppression started within two days. Additional research will determine if the compound is equally effective in other cancers. Therapies that attack tumor blood vessels have recently been a hot area in cancer research because they appear to bypass the major problem with chemotherapy - the tumor cells' ability to mutate and develop resistance to the drugs. - Proceedings of the National Academy of Sciences, 11 June 2002

Scientists removed the glia from the optic nerves of embryonic and 8-day-old rats. The embryonic nerves regenerated 10 times faster than the nerves in the 8-day-old rats. By growing isolated embryonic nerves they established that age was not the key to an axon's inability to regenerate. Rather, they found a signal from the retina told the nerves to stop regenerating. The nerve cells only needed to be in direct contact with one type of retinal cells, called amacrine cells, to permanently lose the ability to grow. - Science, 7 June 2002

Cholera bacteria appear to become even more infectious as they pass through the human intestinal tract, a finding that could help explain why the Third World disease spreads so quickly, researchers say. Researchers found that cholera bacteria isolated from the stools of patients were 10 to 100 times more infectious than laboratory strains when injected into mice. Cholera is spread by feces-contaminated water or food and each year infects as many as 300,000 people in developing countries. The disease causes severe diarrhea that can lead to extreme dehydration and death. Before the Vibrio cholerae bacteria leave an infected person, something, perhaps stomach acid, prompts the germs to switch on a slew of genes. Among them are genes the bacteria need to move and to synthesize nutrients. Other genes that normally restrict the bacteria's movement are switched off. These bacteria become hyperinfectious, so they are more capable of spreading to another person. It is unclear whether the bacteria would be as infectious in humans as they were found to be in mice. - Nature, 5 June 2002

Injections of cells from human umbilical cord blood (HUBC) helped rats recovering from severe traumatic brain injury, researchers have found. It appears that growth factors and messenger molecules from cord blood help promote the brain's self-generated repair of damaged tissue. The study is the first to suggest that human umbilical cord blood may be a novel way to treat such injuries, which are a significant cause of death and disability for adolescents and young adults. These findings were consistent with the therapeutic benefit obtained using cord blood to treat stroke in rats. - Cell Transplantation, June 2002

Drugs currently used to treat Type 2 diabetes may also prove useful for treatment of multiple sclerosis, according to new studies in mice. Two antidiabetic drugs called TZDs, already approved in the USA for treatment of Type 2 diabetes, prevented the development of MS in mice. Other tests are already underway to test if the drugs could also be effective in other neurological diseases, including Alzheimer's, Parkinson's and stroke. The drugs prevented an MS-like disease from occurring in healthy mice and reduced symptoms when given to mice that were already ill. Moreover, the drugs were effective in two different types of the disease, a chronic form in which the mice became ill and remained sick and a model in which the mice developed a relapsing form of the disease, which is similar to the more prevalent form of MS. A clinical trial to test the safety and proper dosage of the drugs in MS patients may start within a year. Even if the drugs are only as good as those currently in use, they still offer an advantage for patients because they can be taken orally. - Annals of Neurology, June 2002

New studies shed light on the mechanism by which nerves are destroyed in multiple sclerosis, and suggest that two chemical messengers called cytokines may lead to potential treatments for the disease. Using mice with experimental autoimmune encephalomyelitis (EAE), that mimics MS, researchers studied how nerves are able - or not - to protect themselves. They discovered that mice lacking the chemical messenger CNTF had a more severe form of the disease. They proposed that CNTF protects special nerve cells called oligodendrocytes against programmed cell death through a mechanism that involves a substance called tumour necrosis factor. Meanwhile, other scientists found that administration of another messenger called LIF can reverse the loss of oligodendrocytes normally seen in EAE. This compound is already known to be well tolerated in humans, and if it has the same oligodendrocyte-protective effects, it may be useful against MS. - Nature Medicine, June 2002

A newly-developed genetically engineered mouse shows symptoms similar to those of human patients suffering from the disease Multiple System Atrophy (MSA), also known as Shy-Drager-Syndrome. MSA is related to Parkinson's disease and up to 100,000 Europeans and 100,000 US-Americans suffer from it. The mouse could help researchers to develop and test new efficient drugs against this widespread disease. Affected individuals either show symptoms similar to those of patients suffering from Parkinson's Disease or have a strong deterioration in their sense of balance. One characteristic of MSA is that some brain cells show abnormal changes. Affected cells that form the isolating outer layer surrounding nerve fibres produce a small protein called alpha-synuclein. Researchers transplanted the human gene for the alpha-synuclein protein into the mouse genome. In patients, the affected cells die as the individual ages, but this does not show up in these mice. The researchers are confident that in a next step they can produce mice that will also show this symptom. This will help us to understand more about the disease and help researchers to develop and test drugs against multiple system atrophy. - EMBO Reports, June 2002

Researchers have found a way of engineering bone marrow cells so that they don't lose their ability to grow into all the different cell types that form bone tissue. When implanted into immunodeficient mice, the engineered marrow cells formed more bone than unaltered marrow cells. This approach is needed because of the poor growth of bone marrow cells outside the body. When cultured in test tubes, marrow cells not only deteriorate and age, but also rapidly lose their capacity to differentiate into all the cell types that make up bone. These problems limit their use as a valuable source of replacement cells for repairing injured or diseased bone. By adding the human enzyme hTERT to marrow cells, researchers showed that prolonged culture is possible and that such cultured cells can differentiate into several different types of bone cells in the laboratory. The studies suggest that hTERT-expressing bone marrow cells may be useful for regenerating bone and possibly other tissues. - Nature Biotechnology, June 2002

A key hypothetical benefit of therapeutic cloning has been demonstrated in practice for the first time. The new experiments in cows show that the technology can prevent the immune rejection of transplanted tissue. To put cloned tissue to a real world test, scientists created cloned bovine embryos from donor animals. They then implanted the embryos into surrogate cows and allowed them to develop further and then harvested tissues from early fetuses. When compared to the donor, the cloned tissues did contain slight mismatches in proteins, enough to hypothetically elicit an immune attack. But in the course of a normal transplant back into the donors, the animals accepted the tissue as their own. For example, cloned kidney cells showed no signs of rejection months after transplantation. The kidney cells were even able to function and produce urine. In contrast, tissue from the fetus of an unrelated animal provoked a strong immune response and was destroyed. - Nature Biotechnology, June 2002

For 2000 years, Chinese medicine has used ginseng root to treat illness. A new study looked instead at the little-known ginseng berry. In mice bred to develop diabetes, an extract from the berry normalized blood-sugar levels, lowered cholesterol levels, improved insulin sensitivity, and reduced weight - by decreasing appetite and increasing activity. Since ginseng berry contains agents that combat both obesity and diabetes, it has enormous promise as a source of new drugs. - Diabetes, June 2002

Acute myeloid leukemia (AML), which accounts for 90% of all adult leukemias, carries a bleak prognosis: the five-year, disease-free survival rate is about 14%. Using mice with AML, researchers have now identified two new drugs that inhibit a specific enzyme that drives development of the deadliest form of AML. AML is caused by a defect in bone marrow cells, which become "frozen" in an early stage of development. The immature cells cannot develop normally and they interfere with blood cell production, causing anemia, hemorrhaging and disruption of organ function. Most adults who develop AML will die from complications related to their disease or from complications of intensive chemotherapy. A deadly form of AML that occurs in about one-third of patients is caused by a mutation in an enzyme called the FLT3 receptor. The researchers showed that two compounds code-named PKC412 and CT53518 were highly effective inhibitors of FLT3. When they gave mice with AML oral doses of the inhibitors, all the mice survived. Clinical trials of are now underway and initial results should be available within a year. - Cancer Cell, June 2002

Scientists have identified a protein fragment, or peptide, that promotes the regrowth of nerve fibers after a spinal cord injury. The encouraging results come from a rat study, but they could point the way to the development of a drug to reverse damage from spinal cord injury, brain injury or some kinds of stroke and multiple sclerosis. There is an inhibitor called Nogo in the brain and spinal cord that stops nerve fibers from growing back after an injury. This lack of nerve fiber growth is the reason why many people become paralyzed after a brain or spinal cord injury. A protein fragment called NEP1-40, or similar molecules, could allow damaged nerves to grow back after spinal injuries, stroke, multiple sclerosis or brain trauma. The peptide blocks Nogo-66, which stops that recovery. So, in rats at least, NEP1-40 promotes significant regrowth in cells in the injured spine or brain. - Nature, 30 May 2002

Transplanting a unique population of muscle stem cells from healthy newborn mice delivers dystrophin, a key protein for muscle function, into mice born with a genetic muscle-wasting disease similar to Duchenne muscular dystrophy. Not only did the donor cells continue to grow and make dystrophin in the recipient, but they also apparently failed to provoke an immune response, and were thus protected from rejection. Scientists isolated stem cells from the muscle of healthy newborn mice that had been grown in culture. Muscle-derived stem cells were injected into the muscles of mdx mice, where they appeared develop into muscle, nerve and blood vessel cells. An added gene marker proved that these cells were incorporated into the musculature of the mice. The cells continued to grow make dystrophin and improve muscle regeneration. Scientists still need to identify a way to deliver the missing dystrophin gene to achieve a global improvement in muscle function. They need to find out the best way to make these cells grow and become the right kinds of cells, as well as to control the process. - Journal of Cell Biology, 28 May 2002

Patients with chronic diseases such as cancer and AIDS often develop cachexia, a life-threatening disorder characterized by extensive weight loss and degeneration of skeletal muscle. The origins and development of cachexia are poorly understood. Scientists have now shown that mice develop a wasting syndrome resembling human cachexia when they are administered high levels of myostatin, a growth factor. Administration of proteins that inhibit myostatin activity, such as follistatin, slowed weight loss in the mice. These results suggest that targeting myostatin may be useful in preventing or treating cachexia, which is estimated to be the ultimate cause of death in about 25% of all cancer patients. - Science, 28 May 2002

Genetically modified mosquitoes are rendered useless at transmitting malaria, at least to mice. The finding shows that genetic manipulation of the insects that carry the malaria parasite could become an important tool for halting malaria transmission. Scientists inserted a gene into mosquitoes that makes a molecule known to block development. The molecule prevents Plasmodium, the malaria mosquito, from moving from the mosquito's gut to its salivary glands. This migration is crucial, as it underpins the transmission of malaria from the blood of one person into another by a mosquito's bite. Inserted into the germ line, the gene is passed on to the mosquito's offspring. Transgenic mosquitoes were at least 80% less effective at spreading a mouse form of malaria. Whether the same gene will prevent transmission of human malaria remains to be seen, and this approach to malaria control is not yet feasible because an inserted gene must persist in the wild mosquito population, and the risks of releasing a genetically modified, and potentially harmful organism into the environment, remain to be investigated. Nevertheless, this work represents a new era of malaria-related research. - Nature, 23 May 2002

Researchers have developed the first animal to mimic the most common type of human leukemia. The genetically modified mouse should enable both a better understanding of the mechanisms underlying the disease, chronic lymphocytic leukemia (CLL), and provide a testing ground for potential new drugs. B-cell CLL often strikes the elderly, and while incurable, is slow growing, often lasting as long as 10 to 20 years. The protein TCL-1 is implicated in several types of human leukemia and lymphoma. The researchers developed mice in which the gene for TCL-1 is put into overdrive in the B cells of the immune system. The hyperactive gene produced too much of its protein product, resulting in uncontrolled expansion of leukemia cells and a disease identical to human B-cell CLL. Because the mouse disease is nearly identical to human CLL, the mouse will enable scientists to investigate all the steps involved in development of the disease. It will also tell researchers whether - and which - drugs work best early or late in the development of the disease. - Proceedings of the National Academy of Sciences, 14 May 2002

A new drug could attack the protein clumps that plague sufferers of human amyloid diseases including Alzheimer's and type II diabetes. In these disorders, normally soluble proteins fold abnormally and become insoluble fibrils that damage tissue. A second protein, called serum amyloid P component (SAP), binds fibrils and makes them particularly resistant to breakdown by the body. Scientists have identified a compound that prevents SAP binding. The compound stops SAP binding to fibrils and speeds SAP degradation by the liver. Amyloid deposits in mice were reduced by administration of the drug. Initial studies have already been carried out on patients suffering systemic amyloidosis, a rare condition in which widespread amyloid deposits are ultimately fatal. The drug drained the stabilizing protein from amyloid clumps. Clinical trials for Alzheimer's sufferers will follow. - Nature, 16 May 2002

New research on cells that produce disease-fighting antibodies in mice helps explain why people succumb more easily to infectious diseases as they grow older. As mice age, they must rely increasingly on B cells that developed during previous infections. In most cases, these 'antigen-experienced' B cells do not fight new disease-causing organisms as effectively as do naïve B cells, which are responding to an infection for the first time. Scientists examined B cells in mice less than 3 months of age and mice older than 22 months, roughly equivalent to studying a teenager a 75-year-old person. One kind of naïve B cell, called a follicular cell, was halved in older mice. In another analysis, results indicated that only one in 20 B cells in young mice were antigen-experienced, as opposed to three quarters of the B cells in older mice. Further studies suggested that transplanting stem cells could restore the B cell population to a younger, more naïve and adaptable profile. - Journal of Immunology, 15 May 2002

The catastrophic failure of a single gene's regulation seems to explain the early death of most cloned embryos, suggests a new study in mice. The gene that encodes the protein Oct4 was misregulated in about 90% of clones from somatic or adult cells. The gene for Oct4 is crucial for embryonic development, and its failure alone could account for the majority of clone deaths. Despite the successful cloning of sheep, pigs and cats, mammalian cloning - in which an ordinary cell's nucleus is transferred to an egg whose nucleus has been removed - remains remarkably inefficient. Fewer than three in 100 cloned mouse embryos survive to birth. The work provides an additional warning against human reproductive cloning. However, it offers new support for the feasibility of therapeutic cloning using embryonic stem cells. The small number of clones that did adequately express Oct4 were capable of forming embryonic stem cell lines. - Genes & Development, 15 May 2002

A team of researchers has cured mice with diabetes type 1 for the first time. In the experiment, the diabetic mice completely recovered from the disease. Although the mice used were genetically modified, the researchers say there should be a gene therapy for diabetics based on this discovery within a few years. The researchers studied the effects of a protein called IGF-I on mice with diabetes, using mice that were genetically modified so that the beta cells in their pancreases would produce the protein. They compared the development of diabetes in these mice to that in control mice without genetic modifications. In the GM mice with IGF-1, the proliferation of insulin-producing beta cells led to complete recovery from diabetes and normal blood glucose levels. - Journal of Clinical Investigation, 15 May 2002

Lung inflammation, damage, and diminished performance caused by radiation of the lungs have been reduced in mice genetically engineered to lack a protein called intercellular adhesion molecule-1, or ICAM-1. These findings suggest that drugs that block the activity of ICAM-1 could be used to prevent radiation therapy-related problems. Therapeutic chest irradiation often results in complications such as lung inflammation, the accumulation of collagen, or scar tissue, in the lungs, and diminished lung performance. These problems limit the ability of physicians to effectively treat lung cancer using radiation. - Journal of the National Cancer Institute, May 2002

A new gene therapy approach can help shrink ovarian tumours and prolong life in mice with the disease. While similar techniques are being studied elsewhere, the new approach overcomes some of the shortcomings of previous attempts and therefore may be more effective. Based on the success of this study, the researchers are hoping to start clinical trials in women with ovarian cancer later this year. The new treatment is injected directly into tumors. The approach uses an inactivated cold virus to "infect" tumor cells with a herpes virus gene called thymidine kinase (TK), which produces the TK protein in the tumors. As a result the tumor cells become sensitive to treatment with the herpes drug ganciclovir and when the drug is administered, tumor cells are destroyed. In essence, this is local chemotherapy targeted to the cancer, sparing healthy tissue. - Journal of the National Cancer Institute, 15 May 2002

Female mice that lack a protein called SCP3 are more likely than normal mice to have a miscarriage, and the risk increases with age, researchers have found. In the study, female mice that were genetically engineered to lack the gene for SCP3 developed normally, but they were much more likely than ordinary females to give birth to small litters because their embryos often died in the womb. Among mice that lacked SCP3, litters were smaller in older mice. It appears that the absence of SCP3 causes chromosomal abnormalities that can lead to miscarriage. Though it is unlikely that many women completely lack this protein, the research may help scientists learn more about how frequently occurring chromosomal abnormalities cause miscarriage. - Science, 10 May 2002

In a finding that calls into question a prevailing belief about the way in which cancers develop and progress, researchers report that it may take only two interlocking genetic steps to cause tumors to develop. In their study, which involved inserting a "switchable" form of the human c-Myc protein into the pancreatic cells of mice, the scientists made three important discoveries. First, they determined that c-Myc harbours a key cancer-preventing mechanism - the ability to cause programmed cell death. Second, they found that thwarting this mechanism by activating another protein, known as Bcl-xL, caused full-blown cancers. Finally, they showed that switching off the c-Myc protein triggered the collapse of robust cancerous tumors - and the blood vessels fuelling them. - Cell, 3 May 2002

Different types of a protein called RAGE may explain why rheumatoid arthritis cripples some people yet leaves others only mildly affected, new research using mice reveals. RAGE (receptor for advanced glycation end-products) is a protein that occurs on cell surfaces in the joints. When RAGE binds other proteins called S100/calgranulins, it is thought to increase the immune response that causes joint destruction in arthritis. Indeed, blocking RAGE from binding to S100/calgranulins in arthritic mice strikingly decreased joint inflammation and destruction, researchers found. They also found that a form of the human RAGE gene that binds its targets more avidly is much more common in people with rheumatoid arthritis. This suggests that different forms of RAGE may partly determine the severity of the disease, and future treatments might be tailored to account for patients' variants. The new results raise the possibility that RAGE is associated with other autoimmune diseases in addition to arthritis. - Genes & Immunity, May 2002

Nerve damage that leads to a loss of sensation and disability in people with leprosy occurs in the early stages of infection. New research shows that this damage seems to be a direct result of the leprosy bug attaching itself to specialized nerve cells called Schwann cells. The damage is characterized by disruption of the myelin sheath, the insulation on nerve cell connections that helps transmit rapid signals between the brain and other organs, for example, skin and muscles. Damage to myelin causes multiple sclerosis, leading to loss of sensation, disability and paralysis. Using laboratory cell tissue cultures and mice genetically manipulated to lack two key immune system cells, researchers showed that Mycobacterium leprae, the bacterium that causes leprosy, destroys the protective myelin sheath that surrounds nerve fibers and then hides out in Schwann cells, poised to initiate later attacks. This novel bacterial mechanism of inducing demyelination may provide clues to early molecular events in diseases such as multiple sclerosis, about which little is known. - Science, 3 May 2002

Researchers believe they are hot on the trail of a way to prevent benign tumors that attack the nervous system and can be precursors to terminal cancer. The research, involving mice, reveals that tumors in neurofibromatosis 1 (NF-1) patients form out of a particular type of cell, the Schwann cell. Neurofibromatosis, also known as von Recklinghausen disease, is a genetic disorder that causes benign tumors to form on the nerves, skin and internal organs. It is the most common neurological disorder caused by a single gene. The benign tumors, called neurofibromas, develop into malignant tumors, called neurofibrosarcomas, in 10-15% of NF-1 patients. The malignant tumors do not respond well to currently available treatments. The new research describes genetically permissive and restrictive environments for NF-1 tumor development. The tumors grow in a permissive environment, but they are nonexistent when the environment is restrictive. The findings could lead to a new approach to combating NF-1. - Science, 3 May 2002

Scientists have mimicked, in mice, sporadic and familial human meningioma, one of the most common types of human nervous system tumors. Meningiomas are tumors of the meninges, the delicate membranes that cover the surface of the brain and spinal cord (most commonly known as the site of inflammation during meningitis). Although the majority of meningiomas are benign, some are malignant. They can occur spontaneously, or are associated with a hereditary disorder called neurofibromatosis type 2. The researchers generated a strain of mice that contained a specific DNA sequence on either side of the gene, NF2, involved in neurofibromatosis type 2. This sequence, when activated by an enzyme, cuts out the genes it encloses. The mice developed using this innovative technology will enable scientists to study the development and progression of meningiomas, and ultimately to test potential therapies. - Genes & Development, 1 May 2002

Isoflavone-enhanced dietary supplements containing genistein may negate the tumor-fighting effects of tamoxifen, a commonly prescribed medication for women with oestrogen-dependent breast cancer, according to new findings. Genistein, an oestrogen-like component found in legume plants, is often identified as one of several desirable isoflavones in soy products, including soy-enhanced drinks and dietary supplements. Researchers monitored the effects of oestrogen and various amounts of tamoxifen and genistein, in mice. Oestrogen and tamoxifen implants were put into the mice and oestrogen-dependent breast cancer cells were injected. Before adding genistein to the diet, the tamoxifen had stopped tumor growth. The addition of genistein resulted in enhanced growth of oestrogen-dependent tumors and increases in oestrogen-responsive gene markers. Blood concentrations of genistein in these mice were similar to those levels that people can get by consuming isoflavone-rich dietary supplements. - Cancer Research, May 2002

Researchers have identified three lung-cancer suppressor genes on chromosome 3 that dramatically reduced human lung cancer growth in mice and for which gene therapy trials with humans will begin within a year. Studying a set of about 20 genes previously identified as possible tumor suppressors, they homed in on a small region of chromosome 3, where they identified eight possible tumor-suppressor genes, and tested six of them for effectiveness on human lung cancers growing in mice. They found three genes that halted tumor growth, induced lung cancer cell death and prevented the formation of secondary cancers. The discovery of this chromosomal 3p region is the earliest genetic change detected in the process of lung cancer development. The finding could provide greater opportunity for earlier detection, diagnosis, prevention and treatment of lung cancer. One of the genes pinpointed in the study, FUS1, will be used in a small trial in which patients with lung cancers will receive the gene delivered in an injected lipid capsule that binds to tumors in the body. - Cancer Research, May 2002

In the first hours and days following a stroke, stem cells leave the bone marrow to help the injured brain repair damage, according to research in mice. Researchers found evidence that bone marrow cells naturally migrate to injured regions of the brain after stroke to help repair damaged tissue; they also become endothelial cells that form new blood vessels and what appear to be new neurons. The researchers are now looking for the right factors to enhance the normal repair mechanism, improve stroke recovery and, since the patient's own cells would be used, avoid issues such as the compatibility of donated stem cells and the ethical controversy surrounding embryonic stem cells. They also want to identify which bone marrow stem cell types are targeted for this repair and how they are called to the site of injury, suspecting that inflammation may be part of this homing process.  - Stroke, May 2002

About one third of breast tumors contain cells that produce too much of a protein called HER2/neu or ErbB2. The chemotherapy drug, Herceptin, blocks this protein and is thus highly effective in treating these cancers. It is widely used in the USA and some European countries, and was approved for use by the UK National Institute of Clinical Excellence (NICE) in March. Undeniably, Herceptin saves lives, but it may in some instances lead to heart failure. The chances of this rise if the drug is given together with other chemotherapy drugs known as anthracyclines. Now scientists have discovered direct evidence that Herceptin causes this serious heart problem. While mice lacking the gene for the protein ErbB2 in their heart muscle appeared normal, their hearts were found to be enlarged and to be functioning poorly. This work suggests that if the effects of Herceptin on the ErbB2 signaling pathway in the heart could be blocked, then this drug would be even more valuable to breast cancer patients. - Nature Medicine, May 2002

Researchers have analysed brain tissue from four patients with multiple sclerosis (MS) and found that the expression of 39 genes was increased, and the expression of 49 other genes was decreased. The researchers then went on to select two of these genes for therapeutic testing in mice with a similar condition to MS, experimental autoimmune encephalitis (EAE). They found that the disease was less severe in mice deficient in an antibody receptor called Fc, and that a compound called granulocyte-colony stimulating factor (G-CSF) improved the condition in mice. - Nature Medicine, May 2002

Nerve cells thought to play a key role in sudden infant death syndrome (SIDS) are located near some of the largest arteries in the brain, according to a study in rats. This supports a new theory that babies who succumb to sudden death (SIDS) have developmental abnormalities in these nerve cells. In healthy infants and adults, the response of these cells to low carbon dioxide levels during sleep may alert them to wake and breathe deeply.  SIDS is the leading cause of death in infants between two weeks and one year of age, striking about one in 1,000 babies. The cause is unknown, but certain risk factors have been identified, including: lying face downward, prematurity, low birth weight, male sex, winter months and recent mild upper respiratory infection. The ultimate goal is to find a way to predict which children are at greatest risk, and find ways to reduce the chance that they will suffer this devastating event. - Nature Neuroscience, May 2002

A synthetic form of bacterial DNA, when administered to mice with inflammatory bowel disease (IBD), reduced the harmful effects of this serious intestinal disorder while enhancing the immune system. Previous studies have shown the beneficial effects of bacterial DNA in treating allergies, but this is the first time it has been used for bowel disease. The results in mice are so promising that doctors hope to begin human clinical trials of the synthetic bacterial DNA. Affecting an estimated one million Americans, IBD includes two closely related disorders that involve inflammation in the intestines - Crohn's Disease and ulcerative colitis. In Crohn's disease there is inflammation deep within the intestinal wall. Ulcerative colitis affects the tissue lining the colon. The symptoms in both diseases are abdominal pain, diarrhea and rectal bleeding. The two disorders are considerably more serious than irritable bowel syndrome, a common intestinal condition that also causes abdominal discomfort and diarrhea. Severe cases of IBD frequently lead to patient surgery involving removal of a portion of the small intestine or all of the colon. - Gastroenterology, May 2002

A new method for tracking immune-cell activity in mice could lead to new drugs for preventing organ rejection. Researchers have shown for the first time that certain T cells may trigger the body's rejection of transplanted organs even without help from the spleen and lymph nodes. The T cell is one of two main classes of lymphocytes (a type of white blood cell), which play a role in the body's immune system. Scientists have long believed that T cells rely on the spleen and lymph nodes to mount an immune response against toxins, bacteria and the foreign blood cells of a transplant. In the new study, investigators discovered that memory T cells, unlike resting T cells, can trigger the rejection of a transplant even when the spleen and lymph nodes are removed. The findings may help improve the success rate of organ transplants. - Proceedings of the National Academy of Sciences, 30 April 2002

The English mastiff dog, a breed that sometimes carries the gene defect for the canine eye disease progressive retinal atrophy (PRA), has been revealed as a key animal to help study retinitis pigmentosa (RP) in humans. Both the canine and human inherited vision disorders involve the loss of rod cells, the photoreceptors in the eye's retina responsible for black-and-white vision and night vision, and a defect in the light-sensitive pigment in the rods, called rhodopsin. One result of the discovery is a new genetic screening test to help dog breeders eliminate the defective gene from their lines of English mastiffs. In the meantime, researchers are continuing studies on dogs with the defective gene - the RHO gene - in hopes of answering a key question for both dogs and humans: what non-genetic or environmental factors cause the disease to progress slowly in some individuals, more rapidly in others and not at all in the lucky few who evidently have the genetic mutation but do not appear to go blind? - Proceedings of the National Academy of Sciences, 30 April 2002

Faulty gene therapy has caused the death of 10 mice from leukemia, during an investigation into potential problems of this innovative technology. It has always been recognized that the viruses used to carry curative genes into patients might accidentally drop their load in the wrong place, triggering cancer-causing oncogenes or disrupting genes that guard against cancer. The mice developed leukemia after receiving mouse bone marrow cells that had previously been altered via gene therapy. Investigation showed the retroviral vector used to load a gene into bone marrow cells had inadvertently carried its DNA into a known oncogene. The overall risk of this happening is very small - previously estimated at one in 10 million - but it demonstrates the importance of continued research and monitoring. So far, around 400 patients have received gene therapy in the UK alone, but only a few were treated with retroviruses. They include two 'bubble babies' otherwise condemned to living forever in germ-free 'bubbles' because their immune systems do not work. - Science, 19 April 2002

Using mice, researchers have found out why a gene mutation prevents the kidneys from working properly. The mutation causes a rare disorder known as nail-patella syndrome, which frequently involves kidney abnormalities. The gene, known as Lmx1b, regulates production of other proteins that are required for normal kidney function. The findings should improve the understanding of nail-patella syndrome and of kidney function and failure. The study found that mutations in the Lmx1b gene cause a reduction in levels of two proteins known as CD2AP and podocin. Both proteins are necessary for kidney cells known as podocytes to mature and function properly. However, exactly how mutations in Lxm1b cause nail-patella syndrome remains poorly understood. The syndrome typically causes misshaped elbows, under-formed kneecaps (patella), and pitted, wrinkled or misshaped fingernails. About 30% of people with nail-patella syndrome also have kidney problems, ranging from small amounts of blood or protein in the urine to progressive kidney failure. - Journal of Clinical Investigation, 15 April 2002

Scientists have discovered a muscle enzyme that, when activated in mice, mimics the effects of exercise without any actual movement. The enzyme, called calmodulin-dependent protein kinase (CaMK), causes muscle to behave as if it has been exercised. Such a drug would improve the lives of chronically ill patients who would benefit from exercise but cannot tolerate the exertion. Mice were genetically modified to make high levels of CaMK in muscle, and even though the animals had not been exercised, their muscles behaved in many ways as if they had. For example, many muscle fibers converted into the 'slow-twitch' type, which has special properties and is abundant in muscle accustomed to exercise. The muscles were better at resisting fatigue during repetitive contractions and had high numbers of mitochondria, the tiny energy factories of cells. - Science, 12 April 2002

A bacterial enzyme that enables severed nerves to repair themselves could form part of future treatment for victims of spinal cord injury. After damage to spinal cord tissue, a thicket of molecules is deposited that prevent nerve cells growing back into the scarred area. Researchers injected rats that had spinal cord injury with chondroitinase ABC, a bacterial enzyme that chews up one of the obstructing molecules. Severed nerves partially regenerated, and the animals regained near-normal walking behavior. In combination with strategies to overcome other inhibitory blocks, chondroitinase ABC could aid recovery from spinal cord injuries. - Nature, 11 April 2002

Researchers have identified a snippet of genetic material that is vital to the development of stomach cancer, a discovery that may lead to a treatment for the second-most deadly form of cancer in the world. A gene called RunX3 prevents the growth of tumors in stomach cells. When mice were genetically engineered with a defective form of RunX3, the cells that line their stomach grew out of control. The researchers also found that RunX3 wasn't working properly in up to 90% of people with late-stage stomach cancer, and in 40% of people whose tumors were in the early stage of cancer. If scientists could find a drug that could reactivate RunX3, it could restore the stomach's natural ability to inhibit tumor growth. - Cell, 5 April 2002

Two genes required for proper development of the brain have some surprising qualities that may help scientists find new ways to treat brain tumors and a variety of other diseases. The genes, known as Olig1 and Olig2, control the development of cells that the central nervous system uses to generate muscle movement. Mice bred to lack one or both Olig genes failed to develop the motor nerves needed to control muscle movement and were completely paralyzed. Smart drugs could be developed to focus on a brain tumor by targeting faulty Olig genes without harming nearby healthy cells. These two genes account for the formation of cells that enable the brain to grow large and complex, an important and crucial step in brain development. Oligodendrocytes, which grow when an Olig gene is activated, surround and protect the nerves with myelin, a fatty insulator. This enables nerves to transmit messages at high speeds over long distances. The loss of myelin leads to multiple sclerosis. - Cell, 5 April 2002

New research in mice suggests that a cell receptor called CD44 promotes healing after lung injury by removing inflammatory cells. Learning more about the anti-inflammatory effects of CD44 could lead to improved treatments for asthma and other inflammatory diseases. The CD44 receptor is known to be involved in removing an inflammation-promoting substance called HA from the site of injury. Researchers studied lung injury in normal mice and in mice that lacked CD44. The normal mice, as expected, completely recovered within two weeks. However, inflammation never subsided in animals without CD44 and these mice died within two weeks. CD44-deficient mice that had their CD44 receptors restored experienced partial healing. The results suggest that CD44 malfunctioning may be involved in some inflammatory diseases and restoring its function could lead to new treatments for inflammation. - Science, 5 April 2002

The identification of a protein in mice that enables the body to overcome resistance to the hormone leptin could help create drug therapies to tackle both obesity and diabetes. Most obese individuals are resistant to leptin, the hormone that tells the brain that our appetites are satisfied and we can stop eating. For this reason, efforts to use leptin in drug form to treat obesity have been largely unsuccessful. In the new research, scientists studied PTP1B (protein tyrosine phosphatase 1B) because they suspected that its absence would increase insulin sensitivity and protection against type 2 diabetes. They produced mice lacking the PTP1B protein that were hypersensitive to insulin as expected, but were also surprisingly lean. In fact, when fed a high-fat diet, the mice gained much less weight and showed markedly diminished body fat compared with a group of control mice. Further testing revealed that the mice expended more energy, comparable to highly trained athletes. This finding offers an approach to overcoming leptin resistance, and provides a target for the development of drugs to treat both obesity and diabetes. - Developmental Cell, April 2002

An experimental anthrax vaccine given by injection or even inhaled could protect against the potentially deadly infection with fewer doses than current vaccines, research in mice suggests. Scientists found that certain formulations of the vaccine fully protected mice against anthrax infection after two doses - whether given via injection, through the nose, or both. The anthrax vaccine currently licensed in the USA requires six shots over 18 months to work, and agencies have been asked to step up efforts to develop a vaccine in pill form or at least one that is effective with fewer shots. Researchers studied various formulations of their vaccine, which consists of a lab-engineered version of protective antigen - the key component in existing anthrax vaccines - encapsulated in a tiny biodegradable sphere. Several regimens completely protected mice from injected and inhaled anthrax. The strongest immune response was seen when the animals were given a vaccine shot followed either by a booster shot or nasal booster. - Infection and Immunity, April 2002

A DNA-based vaccine against the monkey version of HIV has shown some success in protecting animals from the virus. Scientists found that the vaccine for simian immunodeficiency virus (SIV) protected four of seven vaccinated rhesus monkeys from falling ill for more than a year after exposure to the virus. The DNA vaccine - which uses viral DNA rather than a live, weakened virus to elicit an immune response - also induced specific immune responses in the animals' mucosal tissue. Because HIV is largely sexually transmitted, an effective vaccine should ideally elicit a local immune response in the mucosal linings of the body. But any vaccine will also have to protect against the wide range of HIV strains in existence. This study represents the first time a vaccine approach viable in humans - the DNA vaccine - has provided mucosal protection against genetically diverse SIV. - Journal of Virology, April 2002

Scientists have successfully injected genes into rats' brains to reduce or even reverse symptoms of Parkinson's disease in the animals. The genes stimulate the brain to make dopamine, a chemical that is deficient in people who suffer from the debilitating condition. In the experiments, researchers treated rats with a form of Parkinson's disease with injections of three genetic components: two genes that increase dopamine production and a so-called promoter - a section of DNA that enhances the expression of the genes. Animals that received the gene treatment were observed and found to move more normally. Researchers also found an increase in dopamine in the animals' brains. The findings suggest that this treatment may be an effective tool to reduce the effects of Parkinson's. - Proceedings of the National Academy of Science, 2 April 2002

T lymphocytes - a type of white blood cell in the immune system - are vital to bodily defenses against viruses and cancer. T lymphocytes are activated in part by molecules called co-stimulatory signals. However, tumor cells are cleverly able to turn off the effects of some of these signals, thus ensuring their own survival. Recent experiments in mice have shown that hitching a specific antibody to one of the co-stimulatory molecules, 4-1BB, activates it and triggers a strong immune response. Based on this knowledge, scientists developed a form of gene therapy to treat cancer. They inserted a gene for a fragment of the antibody to 4-1BB into mouse melanoma cells and used these 'transfected' cells to vaccinate other mice. The inoculation stimulated the immune system against cancer cells and vaccinated mice were able to reject other tumors. - Nature Medicine, April 2002

The herpes simplex virus (HSV) is responsible for the cold sores and genital herpes that plague a great many people. Fortunately, the introduction of acyclovir in the 1970s offered widespread relief for these conditions. Yet since that time, no new class of anti-herpes drugs has been created - until now. Two new compounds have been developed to thwart the virus. Both target the virus in the same way, but one that is different to acyclovir. While all three stop the virus making DNA, the new compounds do so by blocking the action of a different enzyme. Because they work differently from acyclovir, they may be useful in cases of resistance against acyclovir. The compounds sped the healing of skin and vaginal herpes in mice and reduced the severity and frequency of recurrent disease. Both compounds are more potent than acyclovir and are given by mouth. - Nature Medicine, April 2002

Researchers have cloned rabbits from adult cells. The possibility of targeting specific genes in during the cloning process could make rabbits more useful to model human disease. The scientists adapted established methods for cloning other animals. They first removed the nucleus from a female's egg and then electrically fused it with an adult cell from a donor rabbit, which provided the nuclear material to be cloned. They succeeded in cloning rabbits where others failed because they minimized the time that the fused cells were in the presence of various chemical agents which, while necessary for the cells to start developing, affects later stages of embryo development. In addition, the researchers identified the time necessary for implantation of the embryo into foster rabbits for full-term growth. The resultant cloned offspring showed normal growth and fertility. - Nature Biotechnology, April 2002

Researchers have genetically modified chickens to produce an active foreign enzyme in their eggs - the first real evidence that it is feasible to use transgenic chickens to mass-produce foreign proteins and biopharmaceuticals. A team of researchers inserted a bacterial gene encoding an enzyme into White Leghorn chicken embryos, which when mature laid eggs containing the enzyme. The levels of the protein in fresh eggs remained constant for months and across successive generations, and the researchers plan to develop more robust methods of introducing foreign DNA into chickens to increase the amount of protein made. Based on the results with the test protein, a single hen laying up to 330 eggs per year could produce 17 milligrams or more of a protein drug. As many such drugs are potent, just one egg could yield multiple doses. Unlike other transgenic animals that take years to produce foreign proteins in milk, chickens can start laying transgenic eggs about 21 weeks after hatching. And the foreign proteins should be much easier to harvest and purify. - Nature Biotechnology, April 2002

In mice that develop motor neuron disease (MND) because of a malfunctioning enzyme called superoxide dismutase (SOD1), researchers found that taking away copper had no effect on the pace of the disease, even though it is normally required for the enzyme's activity. Since the 1993 discovery of the enzyme's involvement in MND - also called ALS or Lou Gehrig's disease - it has been thought that copper may be to blame. However, preventing copper from getting to SOD1 didn't make any difference in the onset of disease or survival of these mice. Abnormal aggregates of mutated protein were present, indicating that these mice may be important for further study of the disease. Mutations in SOD1 are responsible for about a quarter of familial, or inherited, MND, and some non-inherited cases as well. Familial MND accounts for roughly 10 percent of all cases. - Nature Neuroscience, April 2002

A bacterium that is harmless in healthy people mutates in the lungs of patients with cystic fibrosis, leading to persistent and dangerous inflammation, according to new research. In contrast to humans, the immune system of mice responds to the bacterium, called Pseudomonas aeruginosa, even before it mutates. In people who don't have cystic fibrosis, P aeruginosa does not typically cause lung inflammation. The bacterium changes the chemical composition of its outer membrane when it invades the lungs of a person with cystic fibrosis. The researchers suspected that this change affects how the body's defenses respond, via a protein called the Toll-like receptor 4, or TLR4. The study results suggest that blocking Pseudomonas aeruginosa adaptation within the cystic fibrosis airway could be beneficial to patients. Whether a drug could be developed to do this is an issue for future research. Understanding interactions and signaling between microbes and animals, such as in this study, is the key to understanding infectious diseases. - Nature Immunology, April 2002

An advance may help produce a test that could one day diagnose Alzheimer's disease at an early stage. In Alzheimer's a protein called amyloid clumps together, and forms "plaques" in the brain, killing brain cells. Researchers studied mice with a particular genetic mutation that made it inevitable they would develop amyloid plaques - although to different degrees. Instead of simply measuring blood amyloid levels, they first injected the mice with a chemical called m266 - which appears to be able to 'draw out' amyloid protein from the brain. Within a few minutes, blood levels of the protein appeared to correlate accurately to the level of plaques formed in the brains of the mice. Such a test could distinguish individuals suffering from Alzheimer's from those with other types of dementia, and may help evaluate an individual's response to particular medical therapies. - Science, 22 March 2002

Scientists have created a new strain of mouse that exhibits cardiac hypertrophy - an enlargement of the heart similar to that which causes heart failure in millions of people each year - and may help explain why men are subject to this fatal condition while women are spared until menopause. The mice were created by "knocking out" the gene that expresses a protein named FKBP12.6 that binds to special receptors in heart cells that control the release of calcium into the cells' interior. Regular spikes in calcium concentrations within cardiac muscle cells cause the heart to beat. What makes these mice particularly interesting, say the researchers, is that they exhibit sex differences in the development of cardiac hypertrophy similar to those in humans. The male mice develop enlarged hearts but the females do not. However, when the females are given a drug that blocks the action of the female hormone, estrogen, their hearts enlarge as well. - Nature, 21 March 2002

Prions, the elusive and mysterious protein particles that cause BSE and CJD, have been detected for the first time multiplying in the muscle tissues of laboratory mice. As a result of the unexpected finding, prion researchers are urging that cattle muscle tissue be studied for evidence of the lethal proteins. In their experiments the scientists inoculated mice with the lethal form of prions and found that they multiplied and accumulated in skeletal muscles - mostly in their hind legs. Although normal mice infected with the prions appear to have remained healthy so far, because the incubation period of the disease is extremely long, a group of genetically engineered mice infected with the prions quickly became diseased and died. At this point, however, the researchers do not know whether the disease-causing proteins could in fact exist or multiply in the muscle tissue of any animals besides laboratory mice. - Proceedings of the National Academy of Sciences, 19 March 2002

Less than a third of people who need a bone marrow transplant find a suitable match, so new research on mice offers the potential to save the lives of thousands of people each year. Mice lacking the gene called SHIP did not reject fully mismatched bone marrow transplants from other mice and most survived without complications following the transplants. The research suggests ways to increase the effectiveness and use of bone marrow transplants from related and unrelated donors; and to treat cancers, genetic deficiencies and autoimmune diseases. In mice, the SHIP gene plays a key role in helping the body distinguish between itself and foreign donor tissue. If the SHIP gene plays a similar role in humans, then drugs to temporarily block SHIP could be given to a patient before they undergo a bone marrow transplant so they won't reject the transplant and the transplant won't attack them. - Science, 15 March 2002

Fibrin, a protein that helps form blood clots, may also be involved in regulating the repair of nerve damage. This discovery could lead to new strategies for repairing diseases of the nervous system such as multiple sclerosis. MS involves loss of myelin, the thin protective coating that insulates nerve fibers in the brain and spine. Previous research has shown that fibrin accumulates in the damaged nerves of people with multiple sclerosis, but the protein's role in nerve repair has not been studied extensively. Now researchers studying mice have discovered that after damage to the sciatic nerve in the leg, myelin regenerated much more rapidly in fibrin-free mice than in normal mice. The presence of fibrin tells neurons and supporting cells that there has been an injury. But the repair process does not start until fibrin stops leaking in from the blood. - Neuron, 14 March 2002

Monkeys that can control computer cursors by thought alone may offer hope for paralyzed people. The research advances previous studies, in which monkeys needed extensive training to complete such tasks and achieved only a limited repertoire of movements. The latest experiments show that activity in the motor cortex of a monkey's brain can be accurately translated by a computer into movement, in real time, of a computer cursor.   Electrodes recorded the activity of a few brain cells in the motor cortex during a series of exercises in which a monkey manually controlled a computer mouse. A mathematical model was built to translate the firing of the brain cells into the cursor's position. Then the monkey played a computer game and after a while the researchers turned off the animal's manual mouse control of the cursor. The researchers say the animal's brain control was nearly as fast and accurate at pursuing a target on the computer screen as the manual control. They believe the system, which depends on an implant in the monkey's brain, is also suitable for humans and could help paralyzed people to work with computers. - Nature, 14 March 2002

For decades, people have blamed a parasitic worm for a disease that has blinded at least 250,000 people now living in Africa and South America. But the real culprit - or an accomplice - may be Wolbachia bacteria that live on the worm. These bacteria are killed by simple and inexpensive antibiotics, which may give doctors working in developing countries an effective tool to attack river blindness. Researchers discovered that the bacteria, which the worms may depend on to reproduce, also stimulate the inflammation that causes lasting damage to the skin and eyes of people affected. They infected some mice with extracts from worms treated with antibiotics, and others with extracts from non-treated worms. Mice exposed to the treated extracts showed significantly less thickening and haze of the eye's cornea, and fewer overall signs of inflammation. Millions of infected patients are normally given the drug Ivermectin, which targets the worms directly. There has been concern that the worms are now developing resistance to this drug. - Science, 8 March 2002

Scientists have linked a gene mutation with nerve degeneration and infertility in male mice. The findings could eventually aid the understanding and treatment of neurodegenerative disorders and infertility in humans. They studied mutant mice known to develop nerve degeneration that hinders movement, sight and sense of smell, and males also have sperm abnormalities that make them infertile. The team discovered that the gene responsible is Nna1, which is expressed in several types of body tissue, including the brain and testes. This gene, which has a human counterpart, is known to be activated when spine nerve cells are damaged. But the researchers also found that mutations in Nna1 were associated with the nerve degeneration and infertility seen in the mice. Mutations in the gene might be related to retinitis pigmentosa or Alzheimer's disease, so studying its functioning further could identify new drug targets for such disorders. - Science, 8 March 2002

Cystic fibrosis is an ultimately fatal disease affecting 1 in 2000 children. It is caused by a defect in the CFTR gene; over 100 different defects are known to occur. Ten years ago research teams bred mice with defects in their CFTR genes and this has greatly assisted progress towards more effective treatments. New research using these mice has shown that a shortened version of the CFTR gene could, with further refinements, lead to gene therapy to correct the human form of this lung disease. The 'mini-gene' appeared to function just like the full gene in laboratory cultures and in mice with CF. These results provide insight into the structure and function of the gene and identify regions that can be deleted without affecting function. Thus they suggest how the gene may be shortened to aid delivery to the lungs in CF gene therapy. - Proceedings of the National Academy of Sciences, 5 March 2002

Scientists have developed a hybrid vaccine that protects mice from West Nile Virus (WNV) infection. The vaccine consists of a weakened combination of two viruses formed by removing key genes from dengue virus and replacing them with WNV genes. Both WNV and dengue virus, carried by ticks and mosquitoes, are similar to the viruses that cause yellow fever, St. Louis encephalitis and other illnesses. WNV occurs in many parts of the world, and although it usually causes only mild symptoms, it can spread to the central nervous system and cause a potentially deadly brain inflammation called encephalitis.  One of the dengue viruses used by the researchers to construct the genetic backbone of the hybrid virus had already been proven safe in people. The researchers therefore hope they will be able to quickly move the new vaccine from tests in monkeys to clinical trials in humans. - Proceedings of the National Academy of Sciences, 5 March 2002

Researchers have demonstrated the ability of transplanted adult stem cells to restore function in rats with stroke. Stem cells were isolated and grown from human bone marrow and transplanted into laboratory rats seven days after a stroke. Before transplantation, the rats were unable to use forelimbs and hind limbs properly. Weeks after receiving stem cell transplants, they regained proper use of their limbs. Previous studies had shown that adult stem cells isolated from human bone marrow could be induced to form different types of cells when grown in tissue culture. In the present study, the transplanted stem cells were found to develop into cells that exhibited the characteristics of the major types of cells found within the brain. These findings suggest that stem cells obtained from adult bone marrow may one day be used to repair the brain and restore function in patients who have suffered a stroke. - Experimental Neurology, March 2002

Mouse experiments suggest that folic acid could play an essential role in protecting the brain against the ravages of Alzheimer's disease and other neurodegenerative disorders, according to a new animal study. Scientists fed mice with Alzheimer's a diet deficient in this vitamin. They found that the mice had reduced numbers of brain cells in the hippocampus, a brain region critical for learning and memory that is destroyed as protein plaques accumulate during Alzheimer's disease. The scientists also discovered that mice with low levels of dietary folic acid had elevated levels of homocysteine, an amino acid, in the blood and brain. They suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the hippocampus. In mice fed an adequate amount of folate, cells in this brain region were able to repair the damage. - Journal of Neuroscience, 1 March 2002

Mice that lack a particular gene are prone to develop benign tumors in the small intestine, and many of these tumors progress to invasive cancer, according to new research. The gene, Muc2, produces one of a group of proteins called mucins, which form mucus on the lining of the intestinal tract to lubricate and protect it. The absence of mucus may expose underlying cells to noxious agents in the food and drink that passes through the gastrointestinal tract. Bowel cancer is the third most common cancer in the UK, and the second leading cause of cancer death. Two thirds of mice lacking the Muc2 gene developed tumors in the small intestine by the age of one year. In younger mice, the tumors were benign, but in the older mice most of them were cancerous. No tumors were detected in normal mice with an intact Muc2 gene. The researchers are now examining how changing the diets of the mice lacking Muc2 affects tumor formation. - Science, 1 March 2002

Juvenile diabetes may have many causes, ranging from autoimmunity to viral infections. Scientists have discovered that the peculiar ability of normal insulin-producing cells to resist infection by coxsackievirus is due to their robust response to natural antiviral compounds called interferons. They showed that interferons are critical in preventing diabetes in coxsackievirus-infected mice. Coxsackievirus damaged the insulin-producing cells of mice when the cells were prevented from responding normally to interferons. The mice developed an acute form of diabetes that resembled that which develops in humans after severe viral infection. Thus, by responding vigorously to natural antivirals, insulin-producing cells seem to play an active role in their own survival. Alterations to the interferon response, which occur after viral infection, may affect the susceptibility of individuals to diabetes. - Nature Immunology, April 2002

Huntington's disease (HD) is an inherited degenerative brain disease that affects thousands of people in western countries and for which there is no effective cure or treatment. HD is due to mutations of the huntingtin gene. The corresponding mutant Huntingtin protein (Htt) is prone to aggregation. It is still unclear whether these aggregates cause loss of brain cells. Scientists have now shown how a protein called arfaptin regulates Htt aggregation. Thus arfaptin may be important in the development of HD and form a target for therapy. They showed arfaptin in cultured cells induces the formation of aggregates containing the Htt protein. They also found increased arfaptin levels in the brain of mice with HD as compared to the brain of healthy mice. - Nature Cell Biology, March 2002

Scientists have engineered immune cells to deliver anticancer gene therapy. Cancer gene therapy has been limited because of undesirable gene expression in tissues other than the tumor, but this approach could complement more traditional cancer treatments such as chemotherapy. To create a gene therapy delivery system more specific to tumors, researchers tailored immune system cells called T cells so that they homed in on tumors and then delivered a relatively harmless prodrug, ganciclovir. An enzyme carried by the T cells converted gancyclovir once inside the tumor cells into a toxin. The scientists showed the success of their approach in tissue culture and in mice with lung and liver secondary tumors. Further studies - for example, to make sure that enough virus is produced by the T cells during their lifetime in the body - will be required before this system can be tested in humans. - Nature Biotechnology, March 2002

As many as half of all human tumors carry a mutation in the p53 gene. This gene applies the brakes at the appropriate time to cells that are dividing, thus when p53 is mutated, or switched off, cells grow uncontrollably. The ability to reactivate p53 activity in tumor cells is an attractive target for anticancer drug development. Researchers have screened several compounds in the search for one that would restore p53 activity. They discovered PRIMA-1, which is able to trigger p53-dependent cell death in human tumor cell lines. Moreover, when injected into mice carrying human tumors, PRIMA-1 decreased the size of the tumors. Because of its ability to restore p53 function, PRIMA-1 may provide the basis for the design of potent anticancer drugs. - Nature Medicine, March 2002

Kaposi sarcoma (KS) is a malignant tumor of the blood vessels most commonly seen in HIV patients. Now, a team of scientists has discovered how protease inhibitor drugs affect these tumors: a finding that may lead to better treatment for KS in both HIV and non-HIV patients. Based on the knowledge that there is a reduced incidence of KS in HIV patients treated with highly active antiretroviral therapy (HAART), of which protease inhibitor drugs are one component, they tested the ability of this particular class of drugs to inhibit angiogenesis (the growth of new blood vessels). They showed that giving two protease inhibitor drugs, indinavir and saquinavir, greatly reduced the growth of KS tumors in mice. These drugs may be useful against a wider range of cancers than just HIV-related KS. - Nature Medicine, March 2002

After the news that Dolly the sheep has arthritis and that cloned mice may have a reduced life-span, scientists report that cloned mice are also prone to adult-onset obesity. They found that mice cloned by the same method used to produce Dolly were heavier than normal after 10 weeks growth. The clones were not simply larger than controls, but displayed all the characteristics of obesity: increased body fat, increased leptin levels, and raised plasma levels of insulin. Importantly, the offspring of these mice were not obese, meaning that the abnormality was not passed on through the generations. It appears that detailed observations of clones may be necessary before this technology is used on a large scale. - Nature Medicine, March 2002

Researchers have identified the gene causing infantile polycystic kidney disease PKD, an inherited form of childhood kidney disease associated with renal failure and death of new-born babies. The researchers were able to identify the gene by first finding a gene that causes a similar disease in rats. Identifying the gene in the rat, and analysing PKD patients, led the researchers to find the human equivalent of the rat gene that is abnormal in this disease. - Nature Genetics, March 2002

Vaccine from Weakened Parasite

Scientists have disabled a common human parasite and prevented it from causing disease by inactivating a single enzyme. This finding could lead to better treatments and vaccines for parasitic diseases such as malaria, which kills two million people worldwide each year. The researchers disarmed the parasite Toxoplasma gondii, which is found in undercooked meat. One dose of the normal parasite is enough to kill a mouse with a suppressed immune system. But when the scientists injected millions of the altered parasites into these mice it did not harm the animals and protected them from infection with the virulent strain. The mutated parasite caused a strong immune response in the animals that could be used to fight other parasitic diseases such as malaria. The insights into parasite-host interactions may also lead to a better understanding of how to develop vaccines for parasitic diseases. - Nature, 21 February 2002

Researchers have expanded on studies of an experimental compound that causes dramatic weight loss and appetite suppression in mice. They now report that lean mice rapidly adjust to daily doses of the drug and get their appetites back, while their obese counterparts do not. The compound, called C75, blocks the action of an enzyme called fatty acid synthase that is found in fat-producing tissues and in the brain, where it seems to be part of an appetite-sensing system. It kills the appetites of lean mice, but only on the first day. Mice engineered to be obese did not eat normally during the entire five days of the study. The scientists will now examine whether obese mice also develop insensitivity to the compound as they approach a normal weight. They also studied mice whose food intake was the same as of the C75-treated mice and found that the C75-treated mice lost more weight. - Proceedings of the National Academy of Sciences, 19 February 2002

A troupe of elderly dancing rats has opened up the prospect of rejuvenating ageing humans. Researchers gave rats a combination of two natural chemicals available in health food shops, an amino acid called carnitine and an antioxidant, lipoic acid. The rats, which in human years were septuagenarians, did better in memory tests and they had more energy. The researchers found that combined together, the two chemicals 'tune-up' the mitochondria, energy-generating power plants in cells. Evidence has been accumulating that deterioration of mitochondria is an important cause of ageing. A significant cause of this deterioration may be the accumulation of destructive free radicals - byproducts of normal metabolism - that disable enzymes and other chemicals. - Proceedings of the National Academy of Sciences, 19 February 2002

Researchers have found a new class of drugs that can cure malaria in laboratory animals. This mosquito-borne disease kills more than two million people, mostly children, every year. The drug, called G25, stops the spread of the malaria parasite by blocking its ability to make copies of itself inside the red blood cells of victims. Small doses of G25 were able to cure infections of two types of malaria in monkeys, and the experiments suggested that the drug has low toxicity. The malaria parasite is becoming increasingly resistant to current drugs. The G25 drug attacks the malaria parasite in a new way, by preventing the parasite from making its fatty membrane, blocking its attempts to multiply. One drawback of the drug is that it must be injected, although it may be possible to develop a version of G25 that can be taken orally. - Science, 15 February 2002

Researchers have reported the first successful use of interleukin-13 (IL-13) gene therapy to treat and prevent rheumatoid arthritis in an animal. IL-13 reduces the production of messengers such as tumor necrosis factor that are involved in joint inflammation. Previous studies have shown that levels of IL-13 are low in the joints of rats with arthritis, as well as in the human rheumatoid joint. In their study, the researchers developed a virus that contains the IL-13 gene. When the virus was injected into the joints of a rat with arthritis, IL-13 was produced, resulting in the suppression of joint inflammation. In addition, injection of the gene into normal rat joints prevented the development of arthritis. - Human Gene Therapy, 10 February 2002

In experiments with genetically engineered mice, researchers have found an "off-switch" for systemic inflammation, the body's overall response to injury and infection. The findings may have implications for treatment of inflammation-related diseases in humans, from asthma to arthritis. Unlike the case in normal mice, in mice bred not to have the "off-switch," an injection of inflammation-causing proteins led to fatal kidney failure, the result of uncontrolled systemic inflammation. Studies have also revealed which genes were affected by the missing off-switch, a protein called stat3-beta. Future studies may prove some of those affected genes, or even stat3-beta itself, to be good targets for treating abnormal systemic inflammatory responses, the researchers say. - Cell, 8 February 2002

Gene therapy has been used successfully for the first time to treat infertility. Scientists corrected a gene defect in male mice, enabling them to father offspring with the help of in-vitro fertilisation (IVF) treatment. Although the research is at an early stage, they believe the technique offers hope for infertile men who cannot be treated at present. The team successfully corrected a defective gene in Sertoli cells, which help sperm to mature. These specialized cells line ducts in the testes and nourish immature germ cells, producing chemical cues that tell them to divide. Mice were genetically engineered to have a defective version of a gene called Steel. When working properly, this gene produces a protein that enables Sertoli cells to swap messages with germ cells. Although the treated infertile males did not produce enough sperm to mate naturally, the scientists fertilized female mice through IVF having extracted semi-matured sperm from the males. - Proceedings of the National Academy of Sciences, 5 February 2002

Scientists have taken an important step towards the use of embryonic stem cells to treat Parkinson's disease. They successfully coaxed immature cells taken from monkey embryos to form brain cells that produce dopamine, a chemical involved in movement that is depleted in Parkinson's. The researchers were also able to make a type of eye tissue called pigmented epithelium, which is the outermost layer of the retina. This tissue can be used to treat retinitis pigmentosa, a degenerative disease of the retina that leads to blindness. With neurosurgeons and ophthalmologists, the scientists will attempt to transplant the dopamine producing cells and pigmented epithelium into monkeys. Scientists previously used the same technique to form dopamine-producing cells in mice. Because monkeys are a lot closer to people than mice, the researchers expect this advance to help research into treatments for Parkinson's disease. - Proceedings of the National Academy of Sciences, 5 February 2002

A team of scientists has genetically modified rats so they develop motor neuron disease (MND, also known as ALS or Lou Gehrig's disease). They rats should speed evaluation of novel treatments, such as those using stem cells, as well as deepen understanding of the fatal disease. The transgenic rat carries an abnormal human gene for an enzyme called superoxide dismutase (SOD1). Faulty SOD1 behavior, caused by a number of different genetic mutations, is at the root of roughly one-fifth of inherited MND cases. So far, the rat has revealed that specialized brain cells called astrocytes play a key role in the early steps of the disease. Astrocytes normally contain a transporter for glutamate, but this begins disappearing in the MND rats, suggesting that the resulting glutamate build-up may be a crucial initial step leading to the death of motor neurons, deaths that directly correspond to symptoms like limb paralysis. - Proceedings of the National Academy of Sciences, 5 February 2002

Scientists have uncovered a major clue to what causes and promotes development of intestinal tumors. Working with genetically modified mice, the researchers found that a molecule called epidermal growth factor receptor (Egfr) is necessary for most intestinal tumors to form. Their work also suggests that a drug could be developed to block the receptor's chemical signaling machinery, which should one day help to treat advanced colorectal cancers in humans. - Proceedings of the National Academy of Sciences, 5 February 2001

By enhancing the brain's natural protective response to the disease, researchers were able to alleviate the uncontrollable tremors and prolong the lives of mice with a neurological disorder that mimics Huntington's. Their finding suggests that a similar treatment strategy may be effective in humans. The mutant Huntington's gene causes the build up of protein aggregates in the brain. An enzyme called transglutaminase that helps these proteins stick together, and a compound called cystamine can prevent this. So researchers treated mice with Huntington's with cystamine injections. The treated mice showed signs of improvement with less severe tremors and abnormal movements, and their lifespan increased by 20%. But to the researcher's surprise, the protein aggregates remained unchanged. The researchers found that mice treated with cystamine had produced more proteins known to play a protective role in the brain. These same neuroprotective proteins are found at increased levels in the brains of human Huntington's patients, suggesting that the brain makes an unsuccessful attempt to protect itself against the disease. In the future, treatments to raise the levels of neuroprotective proteins could be used for Huntington's disease and for other neurodegenerative diseases. - Nature Medicine, February 2002

Severe injury to the spinal cord can lead to paralysis, often with little recovery. The factors that inhibit recovery have thus been a major focus for research. A new study in mice suggests that the key to recovery from severe spinal cord injury may lie in limiting the scarring that generally follows such injury, rather than in trying to enhance regeneration directly. In these mice, a physical block stopping inflammatory cells reaching the injury site limited the formation of scar tissue. Without the barrier of scar tissue to impede them, nerve cells on both sides of the injury site were able to grow and re-establish connections with each other over two to three weeks, leading to substantial recovery of function. The research suggests that drugs able to block scar tissue formation immediately after spinal injury might have a similarly beneficial effect. Perhaps the most tantalizing possibility is that therapies to eliminate existing scar tissue at the site of past injuries might also be helpful. - Journal of Neuroscience, 1 February 2002

Researchers have found that a synthetic antioxidant can delay and prevent the onset of diabetes in mice. In autoimmune, or type 1, diabetes, the immune system mistakenly attacks the beta cells in the pancreas that produce insulin. During the attack, inflammatory cells release oxygen radicals that damage beta cells and eventually cause them to die. As increasing numbers of beta cells are destroyed, the body produces less and less insulin, leading to diabetes. The antioxidant protected insulin-producing beta cells from lethal oxygen radicals generated in diabetes. To the researchers' surprise, the antioxidant also blocked the ability of the immune system to recognize beta cells. The antioxidant, called AEOL 10113, mimics the naturally occurring antioxidant superoxide dismutase. The findings suggest that antioxidants may be useful against diabetes as well as other autoimmune diseases and the rejection of transplanted organs. - Diabetes, February 2002

The health problems associated with obesity include diabetes, heart disease and a shortened life expectancy. Obesity is on the increase and occurs when the body's calorific intake consistently exceeds its needs. One way in which the body tries to regulate food intake is by release of the hormone insulin from the pancreas, enabling cells to convert blood glucose from food into energy. Based on the concept that insulin is able to regulate the body's energy distribution and calorific use, researchers tested the effects of drugs that mimic insulin on rats. These rats become obese when fed a high fat diet. However, treatment with insulin-mimicking drugs reduced food intake and weight gain and, unlike insulin itself, the drugs can be given orally. If these compounds are safe and effective in humans, they may become frontline medicines in the battle against obesity. - Nature Medicine, February 2001

New research shows that the type of anti-rejection drug that organ transplant patients receive could have a direct influence on their chances of developing cancer. Following organ transplantation, patients are treated for prolonged periods of time with drugs that suppress their immune systems. One serious consequence of this treatment is the increased tendency to develop either new or recurring cancers. With this in mind, researchers tested the effects of two anti-rejection drugs in mice with secondary tumors in the liver. They found that mice treated with the newer rapamycin had reduced tumors in the liver, whereas those treated with cyclosporine showed the reverse - increased liver cancer. The scientists believe that rapamycin prevents the development of cancer by blocking the formation of new blood vessels. - Nature Medicine, February 2002

About one fifth of the population suffers from migraine headaches. Understanding the changes that take place in brain cells that cause migraine is essential to the discovery of new methods of treating this incapacitating form of headache. Migraine headache is often preceded by an aura. This consists of flashing lights or shiny angular shapes that drift slowly across the sufferer's vision. After nearly half a century of research, aura is now believed to be due to depression of electrical activity spreading across the surface of the cells in the brain. This so-called cortical spreading depression (CSD) occurs in all vertebrates but has not been linked to the headache that follows an aura until now. In rats, scientists found that CSD activates certain nerves, leading to inflammation in the pain-sensitive meninges, the membranes covering the brain. Therapies that prevent CSD may thus also prevent migraine headache. - Nature Medicine, February 2002

A gene mutation has been identified that results in abnormally low levels of fat in the blood of obese mice. The protein produced by the gene, Angptl3, is thought to regulate lipid metabolism rather than the growth of blood and lymph vessels. The sequence of the human version of the gene is very similar to the mouse version, and variations in the gene may contribute to conditions marked by high cholesterol, including heart disease and diabetes. Targeting the protein may lead to treatments for these conditions. - Nature Genetics, February 2002

In a finding that raises hope for better treatment for Parkinson's disease, scientists have shown that embryonic stem cells transplanted into rat brains will develop on their own to form various brain cells, and that they relieved Parkinson's-like symptoms. Fourteen of 25 rats got better, and when they were killed some months later, these all had new brain cells. This is one of the first solid demonstrations that this can work. However, five rats died with non-malignant tumours at the injection site and the scientists are now trying to prevent this. - Proceedings of the National Academy of Sciences, 19 February 2002

A problem with morphine is that patients taking it for chronic or severe pain - including that caused by advanced cancers - usually develop a tolerance to its effects. Doctors must then up the dose - and the risk of addiction - to keep pain under control. Now researchers, working with rats, have found a potential way to prevent morphine tolerance. Rats given a small dose of a compound called DAMGO along with morphine did not develop tolerance. If confirmed in further studies, the discovery could lead directly to more effective use of morphine. A conventional test of pain-killing effect is to test a rat's sensitivity to heat by exposure to a beam of non-burning laser light directed at its tail. Normally, rats actively flick their tails after a few seconds when they feel the heat. Rats given morphine showed much less sensitivity to the heat, but after four days on morphine they became tolerant to its analgesic effect and flicked their tails, indicating they could feel the heat despite the morphine. But when rats were given both morphine and DAMGO, they felt no heat. - Cell, 25 January 2002

Rare donor organs cannot be frozen and stored for later use - freezing and thawing damage the tissues too much. But scientists have now described the successful transplantation in rats of organs after storage in liquid nitrogen. The organs in question were ovaries with their fallopian tubes attached, and the rats were genetically identical, overcoming the problem of tissue rejection. Although the transplanted ovaries were less efficient after freezing, more than half ovulated normally and one recipient rat became pregnant. If it can one day be applied to humans, the procedure would offer an option to women and children who would otherwise become sterile following chemotherapy. Advances in freezing techniques could also make it possible to store and successfully transplant other organs. - Nature, 24 January 2002

Monkeys immunized with an experimental AIDS vaccine were able to control a subsequent HIV infection as their T-cells were able to attack virus-infected cells. This is a huge advance but there is still a high degree of risk that any virus that lingers in the vaccinated animals could potentially mutate and multiply. - Nature, 17 January 2002

Researchers have genetically altered human blood stem cells to selectively activate genes in developing immune cells. Results of the research in mice show it is possible to transfer genes into stem cells and thus activate the immune system to fight cancer and or tolerate transplanted tissue. - Blood, 15 January 2002

Repeated head injuries increase susceptibility to Alzheimer's disease, but until now it has not been understood how. Researchers found mice that received repeated head trauma - similar to what a professional boxer or football player would experience - developed deposits of a plaque-like protein faster than mice who received a single injury or no head trauma at all. Deposits of this protein, called beta amyloid, are associated with Alzheimer's disease in patients. - Journal of Neuroscience, 15 January 2002

Pointing to possible new ways to combat chronic pain, research in mice shows that a gene called DREAM plays a key role in pain perception. The findings on the DREAM gene could lead to a completely new target for pain control. - Cell, 11 January 2002

Asthma constricts lung airways, leaving patients short of breath, sometimes fatally; it afflicts tens of millions of people worldwide and is becoming more common. Scientists are still struggling to decipher the cellular signals at the root of the attacks. Now, immunologists have described a mouse strain that mimics the human condition and might provide a better model system for studying the disease. The animals' lungs resemble those of chronic asthma patients, with unusually thick layers of collagen and extensive networks of the muscle like cells that constrict airways. - Science, 11 January 2001

Scientists have found that a protein called fibulin-5 plays an essential role in maintaining the elasticity of the skin, lungs and blood vessels. Mice that lack the protein develop loose, sagging skin as well as emphysema and abnormal blood vessels, researchers report. The discovery may lead not only to a better understanding of how wrinkles form, but could also help explain the role played by elasticity loss in diseases such as emphysema. - Nature, 10 January 2002

A diet that contains inadequate amounts of the B vitamin folic acid may raise the risk of Parkinson's disease, new research in mice suggests. The study finds that dopamine-producing cells in the brain, which degenerate in Parkinson's patients, were more susceptible to damage and death when mice consumed a folate-deficient diet. The researchers recommend patients take a 400 microgram daily supplement. - Journal of Neurochemistry, January 2002

Pig Clones Overcome Rejection

A shortage in human organs for transplantation has led to consideration of other species as possible organ donors. The ability to use pig organs has been hampered by the presence of a sugar called alpha gal on the surface of pig cells, which results in their rejection by the human body. Two groups of scientists have separately knocked out one gene for alpha gal in pig foetal cells, and then used these cells to clone pigs. The next step will be to breed naturally from these pigs to create pigs that lack both copies of the alpha gal gene. - Science Express, 3 January 2002

Cancer Defense Implicated in Aging
Too much of a cancer-preventing protein leads to premature ageing in mice, researchers have found. The result suggests that the body may have to strike a balance between preventing cancer and succumbing to old age. The scientists created mutant mice in which the p53 protein is hyperactivated. p53 is one of the cell's key lines of defense, halting cell division, repairing DNA damage and triggering cell death. As expected, the mice developed far fewer tumors than their normal counterparts, but they did not live longer. Their average lifespan was 96 weeks, a reduction of nearly 20%, and their symptoms included weight and muscle loss, hunched backs and brittle bones. This is the first time that p53 has been implicated in ageing. - Nature, 3 January 2002

Surviving Brain Tumors
Research in mice suggests that directly treating tumors with a particular immune system protein may fight a deadly form of brain cancer. Scientists used a genetically modified virus to deliver the protein, interleukin-12 (IL-12), to glioma tumors in mice. They found that the animals that had the IL-12-carrying virus injected directly into tumors survived significantly longer than those given either the virus alone or saline solution. - Cancer Gene Therapy, January 2002

Towards CF Gene Therapy
In an advance towards gene therapy for cystic fibrosis, scientists have partially corrected the genetic flaw behind the disease in mice. Working on cystic fibrosis tissue transplanted into mice, the researchers restored lung cell function to a quarter of that seen in normal cells - a level sufficient to alleviate disease symptoms if it can be achieved in patients with cystic fibrosis. The goal of gene therapy is to substitute normal genes for defective genes associated with disease. The researchers used a harmless adenovirus to carry the correct genetic sequence into cells, where it was spliced into RNA, which then directed production of the correct protein. Although the results are very encouraging, modifications will be required before this RNA-targeted approach can be tested on people with cystic fibrosis. For example, an alternative virus carrier will be needed, because the adenovirus does not readily enter human lung cells. - Nature Biotechnology, January 2002