Southwest Association for Education in Biomedical Research - SwAEBR

Research Focus 2000:

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

 Improving Haemophilia Treatments
Conventionally, haemophiliacs, who lack the blood clotting factors Factor VIII or IX, are treated by frequent direct transfusions of the missing factor. These factors prevent potentially fatal haemorrhages and blood loss. But such treatment is short-lived and expensive, and comes with inherent risks of disease transmission, as was tragically demonstrated in the 1980s when many haemophiliacs contracted AIDS and hepatitis. Two recent studies have shown that alternative forms of treatment might be effective and safer. An implanted device that converts inactive clotting proteins in a haemophiliac's blood into active clotting factors has been successfully tested in rhesus monkeys. An implanted chamber of factor-coated beads provided the required factors for over one month. In a second study, gene therapy using factor IX carried by an inactivated virus looks promising. Previously successfully tested in mouse and dog models of haemophilia, the early stages of a human gene therapy trial are now showing encouraging results. - Nature Biotechnology, March 2000, Nature Genetics, March 2000

Cannabinoids Proven for Multiple Sclerosis
Multiple sclerosis (MS) is a disease of the central nervous system, caused by the patient's own immune system attacking the myelin that insulates and protects nerve cells. MS affects around one million people world wide. Researchers studying a mouse model of MS have found that cannabinoids, the active ingredients in marijuana, may help control the tremors and muscle spasms that people with MS experience. When the mice were injected with cannabinoids, these symptoms improved within minutes and did not return for hours. It was also shown that the cannabinoids stimulated certain receptors on the surface of nerve cells - showing that these are involved in controlling muscles - and did not have a sedative effect. This study confirmed qualitative improvements reported by MS patients in small clinical studies. - Nature, 2 March 2000

Stem Cells Offer Hope for Diabetes
Scientists have reversed diabetes in laboratory mice and the technique may one day be used to cure children of the disease. The researchers grew stem cells - the body's "master" tissue - which enabled diabetic mice to live without regular injections. Although this research is still in its early stages, the results could one day lead to a new way of treating and even curing the estimated 100,000 children who suffer from juvenile diabetes in Britain alone. Scientists isolated the stem cells of the insulin producing tissue within the pancreas and grew it successfully in the test tube over three years. When inserted back into diabetic mice the stem cells made insulin within the pancreas and the animals were able to survive without injections. This raises the prospect of taking pancreatic tissue from a patient in the early stages of the disease and transplanting it in later life when insulin injections would otherwise have become necessary. - Nature Medicine, March 2000

Understanding Brain Tumour Formation
Gliomas are the most common and the most deadly form of brain tumour. What causes them to form is not well understood. In mice, it has been discovered that mutations leading to the activation of two key signalling proteins (Ras and Akt) seem to cause gliomas. Both proteins need to be present to disrupt regulation of cell death, leading to uncontrolled growth of cells and glioma formation. This understanding may lead to the development of new forms of treatment. - Nature Genetics, May 2000

Immune System Boosts Fight Cancer
Most cancers are able to grow and spread because they are hidden from the immune system. Two different types of vaccine have been developed which induced increased activity of CTL killer cells, one of the cancer-destroying weapons used by the body. Both types of vaccine were shown to protect mice against particular types of cancer. - Nature Biotechnology, May 2000

Relieving Bone Cancer Pain
The destruction of bone by cancer cells can lead to devastating pain. A new type of therapy uses a protein to block the formation of cells called osteoclasts which absorb bone material and are present in increased numbers in cancerous bone. Injected into the leg bones of mice suffering from bone cancer, this protein eliminated destructive osteoclast cells and reduced bone destruction and pain. - Nature Medicine, May 2000

Liver Cells Engineered to Produce Insulin
There are probably 30 million diabetics in the world who need to inject insulin to stay alive. Transplantation of the cells of the pancreas that produce insulin is a potential cure for the disease and the subject of intense research. One problem is supply of suitable cells which will not be rejected by the body. Now researchers have succeeded in reprogramming liver cells within the body to produce insulin. In diabetic mice, the liver produced enough insulin to cure them of diabetes. - Nature Medicine, May 2000

Cloned Calves Have Longer Lasting Cells
Six calves have been cloned from foetal calf cells. The cells of these calves show signs of lasting longer and dividing more often than those of calves conceived naturally. This has implications for the study of ageing, and for developing therapies based on stem cells and tissue engineering. It offers hope for degenerative diseases such as Parkinson's and Alzheimer's disease, and even heart disease and diabetes. - Science, 28 April 2000

Huntington's Disease Reversible?
A study using genetically programmed mice has shown that Huntington's disease may be reversible. These mice carry a gene which normally leads to the development of Huntington's disease, but when the gene was "turned off" for four months the disease did not progress. It may be possible to prevent or reverse the deterioration which takes place in middle age in people who have inherited the gene for Huntington's disease, by destroying or inactivating the protein produced by the mutant gene. - Cell, March 31 2000

Rescue from Toxic Shock
Toxic shock is caused mainly by toxins released by bacterial infections, for example from food poisoning or complications of pneumonia. The bacteria which cause it are often resistant to antibiotics, and death may follow within days or even hours. A synthetic protein fragment or peptide, which blocks the activity of the toxins released by the bacteria, has now been developed. When injected into mice the peptide saved all the mice which were exposed to toxins. It also saved about half the animals in which the process of toxic shock had already begun. Untreated mice all died of system failure within days. Tests on pigs, monkeys and then people may go ahead next year. - Nature Medicine, April 2000

Increasing Survival in Motor Neurone Disease
It has been found that mice engineered to suffer from the mouse equivalent of motor neurone disease live longer when they receive injections of an inhibitor of certain enzymes. These enzymes normally act as the cell's executioner in programmed cell death, a process which happens continuously throughout the body. When injected into the spinal cord, the enzyme inhibitor protected the nerve cells, preventing them from being destroyed by the disease. This suggests that programmed cell death causes the destruction of brain and spinal cord nerve cells in motor neurone disease and that blocking this may form the basis of a new treatment. - Science, 14 April 2000

Stem Cells May Restore Sight
Mammalian eyes contain stem cells that could be used to generate new retinal cells in patients with damaged eyes. But growth of these cells in the lab is difficult to control. On the other hand, retinas of fish, amphibians, and some other non-mammals contain stem cells that can easily regenerate. Researchers discovered groups of cells in a specific region of the mouse retina that resemble these stem cells. These cells or their human counterparts may be a potential source of retinal stem cells to treat patients with damaged retinas. - Science, 17 March 2000

Vaccine for Many Cancers?
Vaccination against an enzyme common to many human tumours might mobilise the body's own immune system to attack and kill cancer cells. Telomerase, an enzyme involved in cell replication and key to the uncontrolled replication of cancerous cells, is thought to play a direct role in cancer by allowing precancerous cells to become immortal.
The prototype vaccine activates a type of white blood cell called cytotoxic T-lymphocyte (CTL), to destroy cancer cells using telomerase as a target. It works in breast, colon, lung and melanoma cancer cells in vitro and in transgenic mice which mimic the human immune system and carry human tumours. The mice suffered no side effects. Since telomerase levels in normal cells are low, there is little danger that this approach would cause an autoimmune reaction. This and other potential problems will require further study. - Proceedings of the National Academy of Sciences, 4 April 2000

Smart Mice Give Hope for Learning Disorders
Genetic engineering has produced a strain of super-smart mice which might one day lead to treatments for patients with Alzheimer's disease, mental retardation or age-related memory loss. The mice were engineered to produce extra levels of a protein called GAP-43 which has long been associated with learning. They did much better in mouse maze learning tests than ordinary mice. But the protein had to be manipulated by adding phosphate before it enhanced learning. So finding a way to add phosphate to GAP-43 in humans might provide a way to help impaired learning without resorting to gene therapy or genetic engineering. - Proceedings of the National Academy of Sciences, 20 June 2000

The Perfect Model
Until now, no animal model for Alzheimer's disease has reproduced the full range of symptoms typically seen in human Alzheimer's patients. Researchers have now developed a strain of mice that produces high levels of antibodies against a protein called nerve growth factor (NGF). In adult mice, the level of antibodies is three times that of newborns, and they have only about half of the normal NGF. The mice show all the classic symptoms of Alzheimer's, and should prove valuable in studying the disease and developing and testing treatments. - Proceedings of the National Academy of Sciences, 6 June 2000

Chameleon Properties of Adult Stem Cells
Adult nerve stem cells can give rise to cells in heart, liver, muscle, intestine and other tissues. Adult stem cells were taken from mice and grown with embryonic cells in culture or in chick and mouse embryos. They reverted to an unspecialised state before switching their identity, depending on which cell layer they infiltrated in the early-stage developing embryo. The next stage of this research will be to identify which factors in the cellular environment are crucial in determining the fate of stem cells. It may be possible eventually to create new tissues - avoiding the involvement of embryos - for organ transplants, diabetes or spinal cord injury. - Science, 2 June 2000

Taking out the Trash
Lupus is a common disorder in which the body attacks its own tissues, resulting in arthritis, damage to skin, nerves and blood vessels, and kidney failure. Its cause is unknown, but a contributory factor is thought to be an inability to clear out debris left after cells die. A new study in mice has shown that the absence of an enzyme, DNase1, important in this rubbish removal process, leads to lupus-type symptoms. The gene coding for the enzyme was deactivated and the mice developed symptoms after 6-8 months. New therapies may result from this work. - Nature Genetics, June 2000

New Treatments for Rare Lung Disorder?
Rats with a rare lung disorder have been treated successfully with compounds that inhibit the activity of an enzyme. The disorder, pulmonary hypertension, affects 8 in every 100,000 people and leads to heart failure, respiratory failure and death. Current treatment is with blood-pressure-lowering drugs or heart lung transplant. - Nature Medicine, June 2000

Attacking Rheumatoid Arthritis
A new route for attacking rheumatoid arthritis (RA) has been discovered in studies using mice. This inflammatory disease affects around 1% of the adult population causing severe pain, stiffness, loss of movement and joint damage. It is caused by the immune system attacking the body's own tissues, and the only treatment at present is pain relief medication which also reduces inflammation. In bad cases, joint replacement may be necessary.
Injection of an antibody, anti-CD40, can control progression of the disease. Mice with RA treated with anti-CD40 antibody had reduced joint damage and swelling. These antibodies normally boost the immune system, so the discovery is puzzling. The researchers suggest that the timing of administration of the antibody may be crucial. - Nature Medicine, June 2000

Gene Repair for Muscular Dystrophy
Duchenne muscular dystrophy (MD) is a deadly inherited disease that causes muscle degeneration. Much research into MD has been devoted to gene therapy, but this has proved difficult because the gene is too large to be delivered using viruses or by direct injection into muscles. A new approach to gene therapy has been used successfully in dogs which suffer naturally from MD. This approach, called targeted gene repair used a manufactured molecule containing both DNA and RNA. The molecule caused the cell to use its own repair mechanism to fix the gene defect. - Nature Biotechnology, June 2000

Stem Cells Repair Damaged Nerves
Further progress towards the repair of spinal injury has been made using stem cells. Embryonic stem cells - which can grow into any type of body tissue - were used to obtain a supply of oligodendrocytes, a special type of nerve cell. When transplanted into damaged rat spinal cords and into myelin-deficient mice, these cells repaired damaged nerve fibres by reinsulating them with myelin, the fatty sheath that surrounds healthy nerve cells. These results may also be relevant to other conditions that result in myelin loss, such as stroke and multiple sclerosis. - Proceedings of the National Academy of Sciences, 23 May 2000

Alzheimer Gene Link to Bleeding Strokes
Up to one third of bleeding strokes in the elderly are caused by a condition known as cerebral amyloid angiopathy (CAA). Using mice with a human Alzheimer's gene but without another gene for a protein called apoE, scientists have prevented the build-up of damaging deposits in blood vessels in the brain. These deposits damage the vessel walls allowing blood to leak into brain tissue. One form of apoE, apoE4, is associated with both CAA and Alzheimer's disease in humans. - Annals of Neurology, 1 June 2000

Delivering Gene Therapy
Gene therapy, the transfer of new genes into cells in the body, offers great prospects to treat many diseases such as cystic fibrosis, muscular dystrophy and haemophilia, and even cancers. But one of the difficulties has been finding a vehicle that will deliver genes safely and effectively into the cells' chromosomes. Disarmed viruses have shown promise, but have also raised concerns. Four recent pieces of research using mice have looked at this problem and produced some success. In one, a piece of DNA called a transposon was the vehicle, in another a modified adeno-associated viruses (AAV). Until now, AAVs have proved too small to carry large genes, but the mouse research has shown it is possible to deliver large genes by splitting them in two. Other teams then showed it was possible to use this system to deliver erythropoietin to treat anaemia and Factor VIII to treat haemophilia in mice. - Nature Genetics, May 2000; Nature Biotechnology, May 2000; Nature Medicine, May 2000

Stop the Clot
Levels of cholesterol in the blood are an important cause of the narrowing of blood vessels - atherosclerosis - leading to heart disease. In research using cholesterol-fed rabbits, a new drug called JTT-705 led to beneficial changes to 'good cholesterol' and 'bad cholesterol' in the blood. The drug inhibits a particular protein called CEPT. Researchers now think that this protein, by influencing the level of fats in the blood, may contribute to atherosclerosis. - Nature, 13 July 2000

In the Blood
The inherited blood disorder beta-thalassaemia is common in Mediterranean countries and in much of Asia - in the worst-affected places, such as Cyprus, as many as one in seven people carry the disease-causing mutation. At present, patients can be treated only with regular blood transfusions, iron-purging drugs or donated bone-marrow. Because it is caused by the lack of a single protein molecule, this condition is high on the list of human diseases that might be tackled with gene therapy. But attempts to develop gene therapy to tackle the disease in animal models have been thwarted by insufficient production of the protein. This problem has now been solved in a mouse beta-thalassaemia model. The human beta-haemoglobin gene was successfully transferred into mouse blood stem cells. The resulting bone marrow cells were stable and produced the required protein, haemoglobin, at potentially therapeutic levels after grafting into mice. Similar stem-cell therapies may be possible for other diseases. - Nature, 6 July 2000

Cure for Inherited Blindness?
Retinitis pigmentosa (RP), the commonest form of inherited blindness, is untreatable. But that may change following research using mice with a similar genetic defect. Mice lacking the gene Prph2, which is defective in human RP and macular dystrophy, have damaged photoreceptor cells in the retina of the eye. These photoreceptors regained their normal structure and responded to light when the missing gene was introduced, suggesting that the mice were able to see. This successful introduction of the missing gene into the eyes of mice may eventually lead to gene therapy for human inherited blindness. - Nature Genetics, July 2000

Antibiotic Hope for Huntington's
Mice with a form of Huntington's disease have been treated successfully with a common antibiotic, minocycline. A faulty gene makes brain cells commit suicide, but minocycline puts a brake on this by inhibiting key enzymes called caspases that initiate programmed cell death. It is believed that the antibiotic may also slow cell death in other brain conditions such as Alzheimer's disease and strokes. - Nature Medicine, July 2000

Beating Measles
World wide, one million people died every year throughout the 1990s as a result of measles, representing the largest vaccine-preventable cause of death in children. This is partly because the live-virus vaccine (although safe) is not very effective in babies younger than nine months, and it must be refrigerated, so it is less useful in developing countries. A previous killed-virus vaccine had serious side effects, known as atypical measles. A solution may come in the form of a DNA vaccine, which has been successfully tested in rhesus monkeys, protecting them from infection for at least a year. The vaccine does not need to be kept cold, and, unlike the killed-virus vaccine, did not cause the side effects seen in both rhesus monkeys and in children in the 1960s. - Nature Medicine, July 2000

Heading off Lupus
Systemic lupus is a chronic inflammatory disease that leads to arthritis, anaemia, and damage to the kidney and central nervous system. The exact cause is unknown, but there appears to be a fault with the regulation of the body's defence mechanisms, causing it to turn on itself. Researchers have used a small protein molecule, that interferes with sites in the body where certain antibodies act, to treat a mouse strain that suffers from lupus. Survival increased from 10% without treatment to 80%, there was a decrease in protein in the urine - a clinical sign of lupus - and little evidence of kidney damage. - Nature Biotechnology, July 2000

Transgenic Sheep Clones
An advance in cell technology has resulted in the creation of the first sheep clones whose genes have been selectively modified. The new research has improved on the traditional technique of gene splicing, getting a "foreign" gene to enter a specific region on a chromosome. The researchers inserted a gene that coded for a human protein into a targeted region of DNA in the nuclei of sheep fibroblast cells - the cells that produce collagen. Using the same method that created Dolly the sheep, the modified fibroblast cells were fused with eggs from which the nuclei had been removed, creating clones. These cloned sheep produce a human protein called alpha-1-antitrypsin in their milk. Lack of this protein can cause the lung disease familial emphysema. The technique allows addition, subtraction or replacement of genes at precise locations, which has only been possible before using mice. Thus it should be possible to study human diseases using larger animals such as sheep, pigs or cows, and to produce therapeutic human proteins much more efficiently from their milk or even in hen's eggs. But the immediate aim of this research is the efficient production of genetically modified pigs for animal to human organ transplants. - Nature, 29 June 2000

New Weapon Against Drug-resistant TB
A new type of drug that is effective against drug-resistant strains of tuberculosis in mice and guinea pigs could offer hope for the world's TB sufferers. TB kills more people than any other infectious disease - about two million a year - and over seven million new cases are reported every year. This drug is the first in over 30 years that acts against the TB bacterium by an entirely new mechanism. It is effective against drug-resistant strains because the bacterium has never seen it before. - Nature, 22 June 2000

Repairing the Brain Inside Out
Normally nerve cells only grow in the adult brain and nervous system in extremely limited areas. Now researchers have induced the birth of small numbers of new nerve cells within the brains of adult mice in areas where new nerve cells do not normally grow. They achieved this, paradoxically, by inducing simultaneous destruction of nerve cells, which in turn switched on a whole sequence of genes. These genes orchestrated control signals that directed immature cells to migrate to the right location, to turn into the right sort of nerve cells and to survive. The task now is to uncover the chemical make-up of these natural signals, and to manipulate them to try to increase the rate of production of new nerve cells. If this is possible, then treatments for spinal cord injury or motor neurone disease might result. - Nature, 22 June 2000

Sneaking Gene Therapy into the Brain
Using a fatty coating and precisely targeted antibodies, researchers have found a way to sneak gene therapy into the brains of adult rats. This approach was able to get past the "blood-brain barrier" - a molecular system that keeps many drugs from getting into brain cells. When injected into rats the fat capsule or liposome, linked to the antibody, carried DNA into brain and liver cells. In this case the DNA was simply an experimental "marker" gene that could easily be traced, but gene therapy in the brain or liver might be used to treat or even cure Alzheimer's disease, Parkinson's disease, brain cancer and genetic disorders such as Tay-Sachs and Gaucher's disease. It might also be used in general as a safe and effective technique for gene therapy of all kinds. Gene therapy has not worked well in the past and attempts to make it work in the brain have been particularly unsuccessful. The researchers think their technique might be ready to be tested in humans within months. - Proceedings of the National Academy of Sciences, 20 June 2000

Overcoming Rejection
Pig to human organ transplants provide a possible solution to the acute and worsening shortage of donor organs. While pigs have been genetically engineered to overcome hyperacute rejection, transplantation of tissues and organs into other species still stimulates normal rejection processes. The time taken to reject pig pancreatic cells transplanted into mice has been increased threefold by a novel immunisation technique. After the mice were immunised against a pig protein called CD86, their immune systems could not recognise the protein on the surface of the pig pancreatic cells. Recognition of this protein normally triggers rejection. Rejection eventually occurred after six weeks, but the researchers believe that the technique can be refined to prevent rejection altogether. This approach is directed at treatment of diabetes using insulin-producing cells from pigs, but could also be useful alongside other anti-rejection strategies in whole organ transplants. - Nature Immunology, August 2000

New Mouse Models
The completion of the human genome draft sequence is a major - but preliminary - step in understanding how genes and genomes function. One of the most important tasks that remains is to determine what every single one of the 100,000 (or so) human genes does. Because of the remarkable similarity between mouse and human genomes, this can be done by "knocking out" individual genes in mice and studying the effect. Where the function of genes is known, mouse models of many human conditions, from Alzheimer's disease to sickle cell anaemia, are already being studied. Another approach is to create random gene mutations in mice, pick out the mice which mimic human conditions, and identify the underlying gene defect. This has been done by two consortia who have each generated and screened over 10,000 mutant mice. Several hundred valuable mutant lines have been identified that appear to mimic conditions as diverse as osteoporosis, visual impairment, renal failure, abnormal cholesterol metabolism, spina-bifida, hearing impairment and diabetes. They will be made freely available to academic researchers for experiments to further the understanding of genetic causes of diseases. - Nature Genetics, August 2000

Vaccination in the Womb
A new immunisation technique developed using lambs could be used to vaccinate babies in the womb against infections contracted at, or shortly after, birth. These include serious infections such as herpes, hepatitis B, cytomegalovirus, and two viruses that cause meningitis, group B streptococcus and haemophilus. Such vaccination would avoid the need for caesarean deliveries, infant antibiotic treatment, or maternal treatment with antiviral agents. The researchers gave a single injection of a DNA vaccine against a herpes virus into lamb foetuses in the uterus. The foetal lambs produced high levels of antibody and white blood cells in response. The lambs were normal at birth and developed normally. The nature of DNA vaccines eliminates any risk of infection associated with live- or killed-virus vaccines. - Nature Medicine, August 2000

Iodide to Diagnose and Treat Breast Cancer
Radioactive iodide is used in diagnosis of thyroid diseases and as a treatment for thyroid cancer. Iodide is attracted to the thyroid by a naturally occurring chemical carrier known as the sodium iodide symporter (NIS). Using human breast cancer tissue samples and genetically modified mice carrying human breast tumours, scientists discovered that NIS carries iodide into breast tissue and also into breast tumours. This finding suggests that radioactive iodide may be used in diagnosis and treatment for some forms of breast cancer.
However, the research team did not test whether radioactive iodide would destroy breast tumours in mice. The take-up of radioactive iodide into breast tissue must also be quantified before it can be used to treat human breast cancer patients. - Nature Medicine, August 2000

Earlier Diagnosis for Alzheimer's
Scientists have come up with a promising approach that may allow an earlier diagnosis of Alzheimer's disease, thus allowing earlier treatment. In Alzheimer's disease, protein plaques and tangled fibres build up in the brain, but the only conclusive way to confirm the disease is by observing these in brain sections at post mortem. Using a genetically engineered mouse that suffers from Alzheimer's, researchers have now shown that some of these plaques can be targeted with radioactive labels and identified using imaging equipment. - Nature Biotechnology, August 2000

Fast-acting Flu Vaccine
Variations and mutations in the flu virus mean that it is difficult to protect people against recurring flu outbreaks. The key is to immunise populations rapidly with vaccines against the current spreading virus. While DNA flu vaccines are easy to produce, modify and distribute, the protection they provide is too slow to combat a rapidly spreading infection.
A new type of DNA vaccine has now been developed which overcomes some of the limitations of the previous vaccines. The vaccine protected mice against the flu virus at a dose 10 times lower than the protective dose of conventional forms of DNA vaccine. The implications are important for future flu vaccines and perhaps for other vaccines. - Nature Immunology, August 2000

Rabbit Milk Medicine Saves Babies
Babies have been successfully treated for a rare fatal inherited disease with the help of rabbits milk. Pompe's disease is a fatal muscular disorder caused by deficiency of an enzyme, causing breathing and feeding difficulties, lack of muscle strength and heart problems. The infantile form is rapidly progressive, and babies usually die before they reach their first birthday. Four babies with Pompe's disease received weekly injections of the enzyme, produced in rabbits milk by breeding rabbits with a human gene for the enzyme. The enzyme was taken up by the babies' muscles, resulting in improved heart function and prolonged life. Bigger trials and long-term follow-up are next, to assess final outcome and quality of life. - The Lancet, 29 July 2000

Greedy Mice Stay Slim
Human obesity is a major public health problem in the developed world. For example, an estimated one-third of all adult Americans are overweight. Researchers have genetically engineered mice that can eat far more than normal mice and yet remain leaner and lighter. The mice over-produce the human version of a protein called 'Uncoupling protein 3' (UCP-3) their muscle cells. The protein makes the body burn off energy without making the chemical fuel ATP, producing heat instead. This research could lead to new treatments to combat obesity by finding ways to raise the amount or activity of UCP-3 produced in the human body. - Nature, 27 July 2000

No to Infant Lung Condition
Inhalation of nitric oxide (NO) gas, a therapy that has significantly improved treatment of several life-threatening diseases, also may prevent the development of pulmonary vascular disease (PVD), a dangerous condition that can affect about one of every 500 infants: specifically those who are born prematurely or who have congenital heart defects. Inhaled NO kept infant rats with lung injury from developing PVD by interfering with the basic process underlying the disorder, an overgrowth of cells in the walls of the pulmonary arteries. There currently is no way to prevent PVD in at-risk infants, and treatments for the condition are not very effective. - Circulation Research, 21 July 2000

Smooth-running Joints
Mice with a defective copy of a gene called ank have a disease similar to certain forms of human arthritis. It has now been discovered that this defective gene causes a shortage of a chemical in the joints. This chemical, pyrophosphate, is like a natural water softener, and its shortage leads to abnormal growth of bones that stiffen the joint. A similar gene is present in humans, so in future testing for this gene may reveal whether it is involved in familial forms of arthritis. Researchers hope that these findings may also lead to a new type of drug for arthritis, similar to the antiscaling chemicals in washing powders and toothpastes. But they also warn that arthritis is so complex that a single cure-all is unlikely. - Science, 14 July 2000

Keeping Arteries Clear
Balloon catheters are often used to unblock coronary arteries in patients with heart disease, in a process called angioplasty. But pushing these tubes through the arteries can cause damage, and the body reacts, rapidly laying down new tissue in the artery so that, in time, 40% of angioplasties get blocked again. When this happens, further angioplasty or major heart bypass surgery is required. Using rabbits, researchers have now found that coating balloon catheters with a fat busting compound called ceramide reduced the blockage of arteries following angioplasty by more than 90%. Human trials are expected within the next two years, with enormous potential for saving both lives and health service money if successful. - Circulation Research, 18 August 2000

Two Ways to Clone a Pig
The latest animal to be cloned is the pig, an advance that brings the promise of animal to human organ transplants one step closer. Japanese researchers created a female piglet clone using foetal cells. They injected genetic material into an egg stripped of its own genome and transplanting that injected egg into a surrogate mother. In March this year, a Scottish company announced the birth of five cloned piglets, produced by the injection of genetic material from adult cells into an egg cell without a nucleus. This technique, similar to that used to produce Dolly, the cloned sheep, has now been described in detail on the web site of the journal Nature, prior to publication in the journal itself. In future, researchers hope to genetically modify the cells from which pigs are cloned to obtain a supply of pig organs that won't be rejected by the human immune system. However, there are still worries about virus transmission. New research, again published on the Nature web site, has shown that certain viruses in pig pancreatic cells can infect mice with disabled immune systems. - Science, 18 August 2000; Nature web site, 17 August 2000

Brain Tumours: Seek and Destroy
Human brain tumours such as glioblastomas are among the most difficult cancers to treat. Their tendency to spread throughout the central nervous system often makes surgical removal impossible, and chemotherapy seldom penetrates the blood-brain barrier effectively. New research offers hope for treating such tumours using stem cells. These cells were genetically modified to produce cancer-fighting interleukin, a naturally occurring product of the immune system. When grafted into the brains of mice with brain tumours, the animals had a significantly improved survival compared to animals receiving no treatment. - Nature Medicine, April 2000

Gene Link Between Virus and Heart Failure
A gene has been discovered that leads to a common and highly-contagious viral infection triggering deadly heart disease. The gene called p56Ick allows a coxsackievirus to attack the heart causing heart failure and even death. When exposed to large doses of the virus, mice with the gene develop severe inflammation of the heart muscle and die from heart failure, while those without are completely immune to heart disease. The finding paves the way for future research to predict who is at serious risk of heart disease, and how to prevent it. Coxsackieviruses are part of a common family of viruses that live in the human gut and are highly contagious. An estimated 70% of the population has been exposed to Coxsackievirus B. There is no vaccine against coxsackievirus infections and although the most common result is flu, infection can also cause diabetes, arthritis, meningitis and myocarditis leading to heart failure. - Nature Medicine, April 2000

Flies and Monkeys Aid Progress in Parkinson's
By studying families susceptible to Parkinson's disease, scientists have discovered a gene mutation which causes the disease. Mice without the normal gene also show symptoms of Parkinson's disease. It was shown recently that this mutated gene also causes Parkinson-like symptoms in fruit flies - the flies frequently fall when trying to climb up the wall of a vial. Scientists know a great deal about the genetics of such flies, and they breed quickly, so they may be useful in testing potential drug therapies for Parkinson's disease. - Nature, 23 March 2000

Tests on monkeys have shown that an experimental drug can reverse the memory loss that causes much distress in conditions such as Parkinson's disease and schizophrenia. Such memory loss is caused by shortage of the substance dopamine in the brain, or by blockage of dopamine receptors by antipsychotic drugs. The new treatment is long-lasting, with improvements in working memory and performance for more than a year after the drug was stopped. - Science, 17 March 2000

Blueprinting Meningitis
An effective vaccine was recently introduced against meninigitis C, resulting in a 75% drop in cases. The search is on for a vaccine against meningococcal B infections. Scientists have now mapped the entire genomes of Group A and Group B meningococcal bacteria. Another team has used this information to produce proteins from the Group B bacterium's outer coat to test as vaccine candidates. Seven proteins produced a bactericidal response after being injected into mice. Hib meningitis was the commonest form of the disease until a highly successful vaccine was introduced about 10 years ago. Now Group B meningococcal bacteria are the commonest cause of meningitis and meningococcal septicaemia in Europe, North America and many other parts of the world. New Zealand has been in the grip of a serious epidemic for the last decade. In the UK in recent years there have been about 2,000 cases/year, one in 10 proving fatal. - Science, 10 March 2000

Understanding Alzheimer's Disease
Novel treatments for Alzheimer's disease may result from research using transgenic mice that has revealed why individuals with a certain gene variation are at greater risk from Alzheimer's. The researchers studied mice with the same gene variant and found that it results in the fibres and plaques characteristic of the disease. These fibres and plaques are made of a protein called amyloid beta. Amyloid beta is not thought to be damaging in itself, but this particular gene induces it to form into fibrils and plaques, and it is these which cause brain damage. It may be possible to develop drug treatments which alter the levels in the brain of the lipoprotein produced by the gene, and thus slow or even prevent Alzheimer's disease. - Proceedings of the National Academy of Sciences, 14 March 2000

Inoculating Against Ebola
Ebola viruses cause catastrophic internal bleeding in infected humans. The disease is nearly always fatal and no vaccines or treatments currently exist. Researchers have now found antibodies against an Ebola virus protein that protect mice against infection, despite being given 300 times the lethal dose of virus. The mice survived at least 28 days - the virus normally kills within a week. Some of the antibodies were also effective when given two days after exposure to the virus. The antibodies attack sequences in the protein that are present in all lethal strains of the Ebola virus, suggesting that a single vaccine based on this antibody could protect against all forms of Ebola, even when given after infection. - Science, 3 March 2000