Research Focus 2005:

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

PET Helps Cancer Fight?

Monkeys ID Objects in Milliseconds

Potential New Treatment for Diabetes

Gene Therapy Used to Treat Hemophilia

A virus that typically infects insects could help with the development of gene therapy treatment for hemophilia - a condition in which even a bump on the knee can cause serious internal bleeding in people. Researchers used the virus as a vehicle to carry DNA for a blood clotting factor into the cells of the mice with hemophilia. They found that this caused their liver cells to make a protein that prevents bleeding, and overall it converted hemophilia from a severe form to a much milder form. - Blood, September 2005

Brain Protein Controls Learning

The actions of a protein called reelin that is important to the nervous system have been investigated in mice. Reelin was found to interact with two other molecules, Apoer2 and the NMDA receptor, in an area of the brain known as the hippocampus. This interaction boosts the activity of the NMDA receptors, which eventually results in improved learning. When the researchers created mutant mice that lacked Apoer2, they found that the mice had profound learning and memory difficulties, suggesting that Apoer2 plays a central role in these behaviors. Understanding how Apoer2 functions in the brain and interacts with reelin is critical for gaining further insight into the mysterious mechanisms that cause debilitating neurodegenerative diseases, such as Alzheimer’s disease, associated with learning and memory difficulties. - Neuron, August 2005

New Imaging Technology Detects Diabetes

Researchers have been able to use a new technique to visualize inflammation in the pancreas of mice with type I diabetes – a disease in which the body’s immune system mistakenly attacks its own insulin-producing cells in the pancreas and eventually kills them. Using an imaging method called the MRI-MNP technique, small magnetic particles concentrate around sites of inflammation and therefore allow the high resolution imaging to spot the inflamed areas. In this case, the diabetic mice had inflammation of the pancreas as a result of their condition, so the MRI-MNP technique was able to detect diabetes. It is hoped that the non-invasive approach could be applied to humans for the early detection of type I diabetes and also to assess the effectiveness of potential therapies for the disease. - Journal of Clinical Investigation online DOI: 10.1172/JCI25048, 18 August 2005

BCG Vaccine Destroys Tuberculosis

A third of the world’s population is infected with tuberculosis (TB), and although the Bacillus Calmette-Guérin (BCG) vaccine offers some protection against the disease, it is limited in adults against drug-resistant strains of the bacteria. However, a new formulation of the BCG vaccine has been found to be 10 times more effective than conventional BCG in protecting mice from the TB infection, and also reduced the presence of drug-resistant TB bacteria. These results are promising in the global fight against TB, and it is suggested that it would be most effective to combine both the traditional and the new BCG vaccines. The researchers hope to test these vaccines in humans in 2006. - Journal of Clinical Investigation online DOI: 10.1172/JCI24617, 18 August 2005

Skin Gene May Hold Key to Youth

The gene p63 is considered as the master control gene for the skin, and appears to be the gene that controls the ageing process. In mice the p63 gene was switched off, resulting in premature ageing. The symptoms included becoming hunchbacked, losing hair and losing weight. Loss of p63 also cut short their lives compared with mice with normal p63. The gene may shed light on understanding the ageing process and also in treating ageing caused by some medical treatments.-  Genes and Development online DOI: 10.1101/gad.342305, 17 August 2005

Gene Therapy Eliminates Brain Tumors

A potential treatment for brain tumors has been discovered in a recent study using rats. The most common and deadly form of brain tumor is glioblastoma multiforme (GBM) and usually causes death within 6 to 12 months of diagnosis. These devastating consequences mean that GBM and effective treatments for the condition have been the focus of many research projects. The study involved giving rats with GBM two specific proteins. One is known as RAdTK- a protein that kills cancer cells, and the other is RAdFlt3L – a protein that promotes cell growth in the brain. After receiving this combined therapy, the GBM tumors were completely eliminated and the rats lived for a longer period of time. These results suggest that combined RAdFlt3L and RAdTK gene therapy may ultimately provide an effective treatment for patients with GBM. - Cancer Research, August 2005

Gene Therapy for Muscular Dystrophy

Researchers have delivered a miniature gene, similar to the defective gene involved in muscular dystrophy, throughout the bodies of mice, showing that gene therapy is possible. Rather than having to inject the gene into each affected muscle, the technique used in this study allowed gene treatment throughout all the muscles. As a consequence, the mice with muscular dystrophy showed some improvement. However, there is still some work to be done before this treatment can be used in humans, in particular the method of delivering versions of the defective gene throughout the body needs to be further studied. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0502137102, 15 August 2005

New Gene Discovered for Diabetes

Using a novel technique, the ARNT gene has been linked to the development of type II diabetes. The ARNT gene is known to control the action of many other genes and serves as the master regulator of cell function. Working with mice, scientists found that this gene was expressed at abnormal levels in the pancreas, and when mutations were created in the ARNT gene, the mice developed alterations in insulin secretion that were like those in humans with type II diabetes. These findings provide new insights into the development of the most common forms of type II diabetes and a possible new target for treatment of this disease. - Cell, August 2005

Genetic Clue to Bone and Fat Production

By studying zebrafish, it has been found that a gene called TAZ controls the destiny of adult bone marrow stem cells (MSCs). Since MSCs have the capacity to differentiate into many different cell types, including bone, fat and muscle, this gene is thought to control the balance between bone and fat in the body. When scientists stopped the expression of the TAZ gene, the zebrafish died when they were just eight days old, and failed to form any bones at all. However, in some MSCs grown outside the zebrafish, TAZ depletion caused the cells to readily convert into fat cells. This research presents several therapeutic opportunities, including the possibility that once isolated from the bone marrow, MSCs could be useful for healing bone fractures. In addition, developing a drug to stimulate TAZ activity, could promote bone growth in elderly patients with osteoporosis, and because of its inhibitory effect on fat development, the same drug might also be used to prevent childhood obesity. - Science, August 2005

Enzyme Linked to Childhood Blindness

An enzyme, identified as RPE65, is believed to cause a form of childhood blindness called Leber congenital amaurosis. RPE65 was found to play a crucial role in the development of a visual pigment in the retina, at the back of the eye. The recent study with mice and dogs showed that RPE65 mutations caused blindness, and replacement of the normal RPE65 enzyme restored vision. Mutations in other closely associated enzymes are also thought to cause some types of human blindness, and so researchers intend to study their function, as well as continue to investigate the role of RPE65 in human blindness. - Cell, August 2005

Nasal Vaccine Might Slow Alzheimer’s Disease

Using a nasal spray vaccine, scientists have moved one step closer to blocking the progression of Alzheimer’s disease (AD). The vaccine was tested on mice and combines two medications, known as Protollin and glatiramer acetate, which are currently approved to treat Multiple Sclerosis. Mice with a build up of a brain substance called beta-amyloid plaque were used, since an excessive amount of this substance is known to cause AD in humans. The vaccine was then given to the mice over 6 weeks, and the results showed that vaccinated mice had reduced levels of amyloid plaques in their brains, and importantly none of these mice suffered any toxic side-effects. The researchers are due to begin small-scale testing of this nasal vaccination in humans by 2006, and hope that one day it will be used an effective clinical treatment for AD. - Journal of Clinical Investigation, August 2005

Hope for Stealth Cancer Drugs

A new project has revealed that some drugs can delay tumor growth in animals. The therapy works by firstly using an enzyme to identify the target tumor and then using non-toxic drugs that only become active when they hit the tumor cells. This type of treatment had advantages over the standard chemotherapy treatment used for cancer patients, since chemotherapy can damage healthy cells, as well as tumor cells, resulting in various side-effects like nausea and hair loss. These drugs are a very promising way forward for cancer treatment. Although being more complex than many types of cancer therapies, its selectivity for cancerous cells means that it is a treatment worth exploring. - Journal of Medicinal Chemistry, August 2005

Prostate Tumor Treatment Studied in Mice

Using mice, researchers have discovered a process that could stop the growth of prostate tumors. The mice were injected with special cells from human prostate tumors, which could illuminate under certain conditions. Following this, a genetic treatment that involved molecules known as siRNA complexes, believed to reduce the expression of genes in some cancers, was given to the mice. The results were that luminescence of the tumor cells significantly decreased, indicating that the siRNA therapy was effective at preventing prostate tumor growth. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0501753102, 9 August 2005

Sleep Deaths Better Understood

An ongoing loss of brain cells, known as preBötC neurons, has been linked to deaths where people stop breathing during sleep. The recent work showed that rats that were continuously depleted of preBötC neurons, had breathing problems whilst sleeping, although they seemed healthy when awake. After a few days, the rats completely stopped breathing during REM sleep – the dreaming phase, forcing them to wake up and start breathing again. These problems eventually spread to other periods of sleep and when the rats were awake. Researchers believe that we start life with a few thousand PreBötC neurons and slowly lose them as we grow older, which explains why most breathing-related problems during sleep occur in the elderly. These results could provide clues for future treatments. - Nature Neuroscience online DOI: 10.1038/nn1517, 7 August 2005

Determining the Cause of Diabetes-related Erectile Dysfunction

Findings from a new study suggest that excessive amounts of blood sugar may be the reason why diabetic men suffer with erectile dysfunction. The study examined rats with Type 1 diabetes – the condition when the hormone insulin is not produced – and found that a simple blood sugar, known as O-GlcNAc, prevented the release of certain molecules at nerve endings in the penis that contribute to a sustained erection. Erectile dysfunction is a common problem for more than half the men with diabetes, and since it develops in a different way to non-diabetic erectile problems, it is less effectively treated with conventional drugs like Viagra. Therefore, these results could be a useful step to future treatments for erectile dysfunction in diabetic men. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0502488102, 5 August 2005

Understanding Fragile X Syndrome

Fragile X syndrome is caused by a defect in the Fragile X mental retardation 1 (Fmr1)gene, and can cause serious mental retardation. Recent research has found that mice lacking this gene have problems in certain behaviors which are linked to an area of the brain known as the cerebellum. These mice performed poorly in various motor learning tasks, since these skills are controlled by the cerebellum. Researchers also found that the cells within the cerebellum were abnormal, meaning that they were unable to receive important signals from other nerve cells. This is the first investigation into the role of abnormalities in the brain's cerebellum in Fragile X syndrome, and has led to the conclusion that a lack of FMr1 in cerebellar nerve cells may well lead to problems in human movement in Fragile X patients. - Neuron, August 2005

Gene Therapy to Fight Heart Disease

Researchers have used bone marrow stem cells to fight a severe and sometimes fatal form of heart disease called homozygous hypercholesterolemia in mice. The stem cells were used as Trojan horses to carry a synthetic, therapeutic gene into the liver and prevent narrowing of the arteries. Following the treatment, all of the mice with homozygous hypercholesterolemia appeared healthy and did not show any unwanted side-effects. The next step will be to modify the therapy to treat mice with genetic deficiencies such as hemophilia, and to provide immune therapy against specific cancers, with the ultimate goal being to have safe and effective gene therapies available for testing in humans in two to three years. - Proceedings of the National Academy of Sciences, August 2005

How Do Plagues Disable the Immune System?

Researchers have discovered how the plague is able to outsmart the immune system, in a new study using mice. The animals were infected with Yersinia pestis, the bacterium responsible for mass deaths during the bubonic plague, and after a few days the cells where the bacteria clustered were identified and studied. The results showed that the bacterium injected various toxic substances into the affected cells, ultimately causing cell death. In particular, the cells within the spleen, which mainly consist of immune cells, were filled with the bacteria and their toxic products.  However, researchers have attempted, with some success, to create a potential vaccine for the plague by using a protein on the bacteria, Yersinia pestisuses this protein, known as LcrV, to move the toxic substances into the host’s cells. These findings could be useful for developing effective plague vaccination in animals and in humans. - Infection and Immunity, August 2005

Gene Therapy Prevents Blindness in Mice

A treatment for a rare incurable genetic eye disease that affects boys has been discovered by using mice. The condition, called retinoschisis, arises when retinal cells at the back of the eye stop secreting the protein, retinoschisin (RS1). The absence of this protein means that retinal cells separate and tiny cysts develop. In this study, healthy human RS1 protein was injected into the retina of the right eye in mice that lacked the protein. After six months, they found that the treated right eye seemed healthy, but the untreated left eye showed clear signs of disease damage. This protein transfer method could eventually be used to treat retinoschisis and other genetic eye diseases in humans. - Molecular Therapy, August 2005

Cell Enzyme Causes Cancer

An enzyme known as matripase has been reported to cause cancer in recent mice studies. This enzyme is found on the surface of cells, and can trigger the formation of tumor cells. The researchers produced mice that expressed the human version of the matripase gene in a stable, readily measurable manner and found that these some of the mice developed advanced cancerous tumors. In addition, the study revealed that cancer-producing chemicals present in tobacco products were dangerous in combination with matripase over-production, since these chemicals increased the chances that tumors would turn cancerous. Matripase obviously plays an important role in cancer formation and will have a lot more to tell us about human health and disease in the coming years. - Genes and Development, August 2005

Stem Cells May Lead to Brain Cancer

Studies in mice have shown that certain types of brain tumor may be initiated by primitive stem cells. Unlike adult stem cells, which are already programmed to become certain types of tissue, some primitive stem cells could be predisposed to form tumor cells. The scientists bred genetically engineered mice that lacked a gene called p53, known for its role in preventing tumors by repairing the errors in DNA that can result in cancer. The mice also had a mutated version of another tumor suppressor gene called NF1. As these mice matured, they all developed brain tumors, and it was found that stem cells in a certain part of the brain gave rise to the cancerous cells. This could help explain why brain tumors are so hard to cure. Surgery and radiation therapy may remove the tumor, but the cancer could be replenishing itself from the stem cells. - Cancer Cell, August 2005

Protein May Yield Anti-obesity Drugs

New findings from a study with mice suggest that the protein SH2-B might underlie obesity in humans.SH2-B keeps the brain sensitive to the fat hormone, leptin, which sends signals to the brain about the body's fat content. This in turn decreases appetite and increases energy expenditure to maintain normal body weight. Mice lacking SH2-B were found to overeat and become obese. The animals also had high blood concentrations of leptin, insulin and lipids and developed fatty livers and high blood sugar. Elevated leptin levels are a hallmark of leptin resistance, a primary risk factor for obesity. Drugs that mimic or enhance SH2-B action may improve insulin and leptin sensitivity and have potential value in treatment of obesity and type 2 diabetes. - Cell Metabolism, August 2005

A New Diabetes Treatment?

Researchers have discovered that increasing the concentration of a key regulator involved in glucose metabolism can improve the way the liver produces and disposes of glucose in mice. In this study, scientists increased the concentration of the regulator molecule, called fructose-2,6-bisphosphate, and found that the mice's blood sugar went down. The mice were using more and producing less glucose. In addition, when the concentration of the regulator was increased, there were changes in food intake and overall metabolism. It caused food intake to decrease and energy expenditure to increase, so weight loss occurred. If the level of this regulator in the liver of humans can now be raised, for example, by preventing its breakdown, it could lead to a new treatment for diabetes, as well as obesity. - Cell Metabolism, August 2005

Protein Points to New Therapies for Diabetes

A new study has found that a protein called Sirt1 has implications in the regulation of type II diabetes – a condition where patients clear glucose more slowly than non-diabetics. Mice that were designed to over-express Sirt1 in pancreatic cells produced more insulin and cleared glucose from their bloodstreams significantly faster than the normal control mice. Sirt1 is probably a very important regulator of various cellular responses to different types of nutrients, such as glucose and fatty acids. Continued research in the lab will use the mutant mice to further investigate Sirt1's role in these responses in type II diabetes. - Cell Metabolism, August 2005

Vaccine May Protect Against E coli

An oral vaccine consisting of bacterial ghosts, or empty bacterial envelopes, may protect against E coli in animals and humans. E coli is a bacterium that can cause severe intestinal inflammation, and more importantly is associated with several life threatening diseases in humans. In this study, mice were given the oral vaccine, followed by a lethal dose of E coli several weeks later. These mice had a significantly higher survival rate than the infected mice that had not been given the vaccine. This method of vaccination with new, improved nonliving bacterial vaccines should be much safer and could be used to prevent the development of E coli infection in humans. - Infection and Immunity, August 2005

High-fat Diet Blocks Response to 'Stop Snacking' Signal

According to a recent study, a high-fat diet can make rats less sensitive to the hormone that limits food intake. Rats fed on a high-calorie and high-fat diet were less responsive to the hormone, known as CCK, which usually activates the nerves connecting the intestine to the brain and suppresses eating behavior. When doses of CCK were given to rats fed on a low-fat diet, however, their intake of food was significantly suppressed. These results link in with previous studies in humans, which show that people who eat a diet rich in fat have more CCK in their bloodstream, but are less responsive to it. This leads to feelings of persistent hunger and therefore more eating. Studies like this are important in understanding obesity – a condition which in becoming increasingly common in society today. - Journal of Nutrition, August 2005

Immune System Rejuvenated by Common Hormone

The sex steroid, Luteinizing Hormone-Releasing Hormone (LHRH), has been found to play an important role in immune system function. Blocking the release of this steroid in mice, led to growth of the thymus – the organ which produces immune cells (T cells) to fight infection. This occurred as a result of improved production of stem cells in the bone marrow, which provided the fuel to revitalize the thymus and increase production of immune cells. The treatment could be beneficial to patients recovering from bone marrow transplants, who are susceptible to infections, cancer patients receiving chemotherapy or radiotherapy that depletes the immune system, as well as patients suffering from HIV/AIDS. - Journal of Immunology, August 2005

Spare Bone Grown on Shin

New bone tissue has been grown on the surface of rabbits’ shin bones. Scientists allowed the tissue to mature for 6 to 8 weeks, after which it was used successfully to repair injured bone elsewhere in the rabbit's body. This advance means that rejection-free bone tissue could become available for transplants in the future, if these methods can be adapted to humans. It could revolutionize the treatment of conditions that range from bone cancer to chronic back pain, and fractures to reconstructive surgery. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0504705102, 29 July 2005

Natural Sweetener May Encourage Weight Gain

Researchers have found that fructose – the natural sweetener used in many soft drinks – contributes to weight gain. Mice drank either plain water or fructose-sweetened water and soft drinks. Those that drank fructose had nearly twice as much body fat as those that drank just plain water. However the mice which drank the fructose-sweetened beverages ate less food than the other mice, so did not consume more calories overall. Thus the staggering increase in weight due to fructose intake is an important finding, particularly for those involved in attempting to combat the rising obesity crisis. - Obesity Research, July 2005

Cells Restore Egg Production

A research team says it has found a group of cells which can replenish the ovaries of sterilized mice. The procedure involved using a cancer chemotherapy drug to destroy the eggs in the ovaries of the mice. When they were assessed two months later it was found that their ovaries looked normal. The cells responsible for this restoration were thought to lie within the bone marrow, so bone marrow cells were taken from healthy mice and injected into infertile mice. Again, after two months the ovaries of the infertile mice looked normal. These findings could help explain previously mysterious cases of women sterilized by cancer treatment who spontaneously became pregnant after receiving bone marrow transplants. However, further work is needed to confirm that similar cells exist in women and that they can safely restore fertility. - Cell, July 2005

Gene Pattern Cancer Spread Clue

Researchers have traced some important genes in mice which control whether breast cancer can spread to the lungs. They injected mice with cancer cells from a patient with aggressive breast cancer, and observed which cells migrated to their lungs. The genetic make-up of these cells could then be analyzed. They identified 54 genes that were associated with the development of secondary tumors in the lungs, and they also found that some genes functioned more vigorously than normal. This suggests that the ability of a tumor to form a secondary tumor elsewhere in the body depends on the combined actions of multiple genes. In this case, by targeting these genes with drugs, it could slow the growth of the primary tumor in the breast and prevent the spread to other areas like the lungs. - Nature, July 2005

Smart Bomb Zaps Cancer Cells

A molecular anti-cancer bomb has been developed in mice to treat tumors. The miniature device is like a double-skinned balloon and is called a nanocell because it is so tiny and similar in design to a living cell. The bomb was injected into the bloodstream of the mice with skin and lung cancer. It , was able to travel deep into the tumors and release chemotherapy drugs and other drugs that can disintegrate the blood vessels within it, causing the tumors’ destruction. Mice given this treatment survived three times as long as untreated rodents. Since the drug-packed bomb explodes inside the tumor, healthy cells are unaffected and remain intact, which eliminates debilitating side-effects such as nausea, vomiting, weight and hair loss. Researchers believe that this technology could be effective for cancer therapy in humans and could be adapted to treat other forms of cancer. - Nature, July 2005

Gene and Stem Cell Therapy for Spinal Cord Injury

Gene therapy using a combination of stem cells can promote new growth of the insulation material around nerve fibers in the damaged spinal cords of rats. A new study provides the best evidence so far that the production of the nerve-insulating substance, known as myelin, can lead to substantial improvements in the ability to walk and overall co-ordination in the animals with spinal cord injury. The combination of stem cells with specific proteins called growth factors was crucial in this repair, since those rats treated only with the stem cells did not show significant improvements following spinal cord damage. The research team is now focused on developing a similar kind of therapy for humans. - Journal of Neuroscience, July 2005

How Trauma Triggers Long-lasting Memories

Research on rats could help scientists to understand why emotionally-arousing events are remembered more vividly than emotionally-neutral events. Stimulation of the emotion center of the brain, the amygdala, caused an increase in the levels of a protein called Arc in the brains of the rats. This increase was particularly prominent in a brain area known as the hippocampus, which is involved in the processing and storage of long-lasting memories. Thus, more Arc protein was produced in the hippocampus only if an experience was emotionally arousing, or important enough to activate the amygdala and to be remembered days later. These findings indicate that the amygdala plays a pivotal role in remembering emotional experiences, and gives a new insight into the way long-lasting memories are stored. - Proceedings of the National Academy of Sciences, July 2005

Testing Potential HIV Vaccines

Using macaque monkeys and computer simulation studies, scientists have been able to more closely replicate how HIV infection develops in humans. They found that repeatedly injecting the animals with low doses of the HIV virus was more akin to how humans are exposed to HIV. Importantly, they showed that their methods required far fewer animals than previously thought.  These types of study play an essential role in evaluating the effectiveness of potential HIV vaccines and treatments – the development of which is a major goal of AIDS research. - Public Library of Science Medicine online DOI: 10.1371/journal.pmed.0020249, 19 July 2005

Carbon Monoxide: Poison Gas or Anti-inflammatory Drug?

Inhaling carbon monoxide (CO) prevents transplant rejection in mice, a new study has revealed. Scientists found that giving small amounts of the gas to the mice for inhalation prevented the development of a lethal inflammatory reaction following transplantation of the trachea, or windpipe.
This has implications for patients, since CO could prove to be a life-saver in those recovering from organ transplants. However, although these findings are positive, there are still serious issues about the dosage and toxicity of CO to use in potential treatments, because in this study small amounts seemed to be beneficial, but a little more could cause death. - Journal of Experimental Medicine, July 2005

Shedding Light on How Humans Age

Mutations in certain genes can cause mice to age twice as fast as normal mice. Mice usually live for about 3 years, but the mutated mice were found to live for an average of only 14 months. The genetic modification caused more errors in the DNA of the mouse cells to accumulate over time compared to normal. Since these mice lived for approximately half the normal time of normal mice, it suggests that the genes affected by the mutations play a central role in the mechanisms of ageing. This research is a valuable piece in the puzzle of ageing, and could help scientists understand why different species have different lifespans. - Science DOI: 10.1126/science.1112125, 15 July 2005

Protecting Against Clogged Arteries

The ability of the blood to clot depends on a number of proteins, called clotting factors. These are essential since too little clotting can lead to bleeding disorders and too much clotting can block blood vessels leading to strokes and heart attacks. However, a new study using mice has revealed that lacking a particular clotting factor may protect against clogged arteries, without causing excessive bleeding. Scientists found that mice lacking factor XII (or Hageman factor) did not develop blocked arteries in response to blood vessel injury. These results are consistent with human studies where it was found that elevated levels of factor XII led to increased coronary artery disease. It is now thought that drugs which can prevent this protein from functioning normally may be useful for treating various types of heart disease, without the risk of spontaneous bleeding. - Journal of Experimental Medicine, online DOI: 10.1084/jem.2005066411 July 2005

Bone Marrow Cells Make Muscle Cells

Researchers have transformed ordinary bone marrow cells from rats and humans into fully-functioning muscle cells. The isolated bone marrow cells were firstly exposed to specific molecules and genes to promote their growth, and it was found they were able to differentiate into skeletal muscle cells. These cells were then injected into mice and rats that had been induced with muscular dystrophy, and it was observed that the cells grew into muscle fibers, which were able to promote muscle regeneration in the condition. The success of this study means that more effective treatments for muscular dystrophy may be possible in the future. In addition, this type of cell regeneration could prove to be useful in treating other degenerative conditions, such as Alzheimer’s and Parkinson’s disease. - Science 8 July 2005

Crib Death Discovery Breakthrough

In a new study using rats, scientists have been able to identify the brain chemical that triggers the body to breathe more quickly and deeply during exercise. When carbon dioxide levels rise, it was found that the chemical ATP is released from various brain areas, and seems to control our breathing rate in accordance with our metabolism and activity. The release of ATP is believed to optimize breathing to boost maximum performance. This discovery could be used to study ways of stimulating breathing, and may help in understanding certain breathing disorders, such as cot death and chronic airway disease. - Nature 7 July 2005

Trigger for Huntington’s Disease Found

An abnormal protein produced in Huntington’s disease activates the regulatory p53 protein, a recent animal study has revealed. The p53 activation is thought to damage and kill brain cells, not only playing an important role in Huntington’s disease, but also in Parkinson’s disease and motor neuron disease. In groups of mice with Huntington’s disease, researchers found that p53 increased cell death. However, removing the p53 protein from the Huntington’s mice reversed the behavioral abnormalities that they would otherwise display, such as abnormal reflex responses. These findings provide further clues to the mechanisms behind Huntington’s disease, as well as a link between various types of cell damage in the condition. - Neuron 7 July 2005

Retina Seeks the Unexpected

By recording signals from the retinal cells of salamanders and rabbits, scientists have found that the retina is more sensitive to novel and dynamic images, rather than common images. The retinal cells which convey information from the eye to the brain are known as ganglion cells, and these are thought to adjust after just a few seconds in a new environment, allowing the cells to pick out unusual features in the image. The study suggests that this response is typical in both amphibians and mammals, since the sensitization of retinal cells to novel scenery occurred in both salamanders and rabbits. - Nature, 7 July 2005

First Exposure to Smells Alters Brain Development

The first odors that newborn rats smell appear to govern their brain development. These early experiences are thought to alter the number of various types of receptors that respond to brain chemicals in a part of the brain known as the olfactory cortex - an area essential for detecting and recognizing smells. To test for this, researchers blocked each nostril of the newborn rats in turn, and compared the activity in both sides of the brain. They observed a decrease in NMDA receptors, which respond to the brain chemical glutamate. Due to the complex function of these receptors, researchers believe this reduction could be responsible for ‘olfactory imprinting’ – the process of developing a strong attachment to maternal odors that occurs early in mammalian development.  These results can now point scientists in the direction of identifying the critical period in the development of the olfactory system. - Neuron 7 July 2005

How HIV Disables Cells’ Call for Help

Findings from studies using rats have revealed how a fragment of the HIV protein is able to shut down the body’s normal immune response. The fragment, known as fusion peptide or FP, was found to lock onto several proteins involved in the immune response, preventing its ability to function correctly. However, researchers also believe that these FPs could be useful in treating autoimmune diseases, where the body’s immune response becomes overactive and attacks its own cells. This was confirmed when the group tested FP on rats with a type of arthritis and found that they showed a significant reduction in joint swelling and other associated symptoms. Therefore, by using FP in humans, overactive immunity could be better controlled. - Journal of Clinical Investigation, online DOI: 10.1172/JCI239567 July 2005

Possible Stroke Drug May Aid Brain Cells

A new drug, known as SB-3CT, has been found to significantly reduce the extent of brain damage in mice with an animal version of stroke. Initial tests showed that these mice had only 30% of the damage that occurred in another group of mice who were only given the standard current treatment for stroke. This treatment is called tissue plasminogen activator (tPA), and is at present the only medical treatment approved for stroke. However, it is limited in its use, because to be effective it has to be given to patients within three hours of the attack. The use of SB-3CT alone, or in combination with tPA, may avoid the limitations of current therapy and could allow the development of a new generation of drugs for stroke. - Journal of Neuroscience July 2005

Nerve Chemicals May Offer Early Cancer Diagnosis

A chemical which nerves produce to communicate with each other, called GABA, is present in unusually high amounts in some aggressive tumors, according to a recent animal study. It was found in excessive quantities in aggressive prostate tumors in mice, and researchers now believe that tumor cells use GABA to signal to each other and to the environment. By exploiting this signaling pathway and interrupting GABA transmission, it is hoped that existing drugs which are able to do this may provide some therapeutic benefit for patients with these forms of cancer. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.05007561025 July 2005

Gene That Determines Asthma Susceptibility

The absence of the Nrf2 gene has been found to increase the number of inflammatory cells within the airways, causing the airway lining to swell which induces asthma in mice. Nrf2 is crucial for normal responses to allergens in the lungs and controlling the release of specific unstable molecules by inflammatory cells, which are responsible for restriction of the airways. It seems that the presence of Nrf2 would therefore interrupt the inflammatory responses in asthma. This research may hold clues to better control of inflammation in asthma, and future studies will now focus on the molecular mechanism underlying the regulation of asthmatic inflammation by Nrf2. This may determine whether targeting Nrf2 could result in a significant new treatment for asthma. - Journal of Experimental Medicine July 2005

New Treatment Target for Epilepsy

Researchers have learned more about the potential brain pathways involved in various types of childhood epilepsy in a new study with ferrets. Epilepsy begins with hyperactivity in areas of the brain, known as the cerebral cortex and thalamus, with the abnormal electrical discharge then spreading to other parts of the brain. The release of the brain chemical glutamate is known to be largely responsible for the high-intensity activity, but this study revealed that special cells regulating the release of glutamate also exist within the thalamus. In epilepsy patients, it is thought that this regulatory function, which is able to slow glutamate release, may not function correctly. Therefore, a treatment that is able to target these cells could potentially block the pathway associated with epileptic seizures. - Journal of Neurophysiology July 2005

Eye Allergies Threaten Corneal Transplants

Corneal transplant patients who suffer from eye allergies are at a significantly higher risk of transplant failure than those without allergies, a new mouse study shows. Scientists found that the immune system's response to corneal transplants was profoundly elevated in mice with allergic eye disease, resulting in the rejection of all corneal grafts. This was in sharp contrast to the 50% rejection rate that occurred in the mice without allergic eye disease. Moreover, transplant rejection was faster in the allergic group. The study confirms clinical observations that patients with eye allergies have a significantly higher risk for rejecting corneal transplants than patients without eye allergies, and clearly suggests that allergists and ophthalmologists need to work as partners in managing allergic patients destined to receive corneal transplants. The finding stands previous theory on its head – proteins associated with allergic responses are known to inhibit immune cells and thus were previously believed to prevent graft rejection. - Journal of Immunology, 1 June 2005

Older Mothers Have Shorter-lived Children

Delayed motherhood in mice results in shorter life expectancy and reduced body weight in their offspring. It is already known that late maternal age in women carries the risk of chromosome abnormalities such as Down’s syndrome. However, other potential negative effects on offspring from delayed motherhood have until now been only anecdotal. Several other aspects of reproductive fitness of offspring were assessed in the current study, but none showed significant deleterious effects. The report is expected to stimulate research into the mechanisms that result in these disturbing consequences. - Biology of Reproduction, June 2005

A Potential New Stroke Treatment?

A new pathway to necrosis, a form of cell death, has been discovered in a mouse model of stroke. Necrosis is a common feature of human brain diseases from stroke to neurodegeneration and, unlike apoptosis (a precisely orchestrated pathway to initiate cell death), was generally believed to be a passive cellular response to external damage. Now, scientists have found a previously unknown cellular pathway leading to necrosis, which they call necroptosis. The team demonstrate its involvement in conditions where not enough blood reaches the brain. A growing number of studies had reported evidence for non-apoptotic cell death with some features of necrosis, but scientists have had no tools to investigate the potential mechanisms behind these observations. To address this, the team identified a chemical, necrostatin-1, which specifically and invariably inhibited this non-apoptotic cell death. They then found that it reduced ischemic brain injury in a mouse model of stroke. It is therefore a promising therapeutic lead for treating patients with brain injury following stroke. - Nature Chemical Biology, online DOI: 10.1038/nchembio711, 29 May 2005

A new mechanism behind atherosclerosis

Although smoking and elevated cholesterol levels have been shown to increase vascular disease, many patients do not have these risk factors. Research using mice offers a clue. The mice were genetically modified to overexpress a gene that disrupts energy production from respiratory oxygen in blood vessels. This caused a rise in oxidative stress in the walls of arteries, leading, in turn, to a rise in blood pressure and to hardening of the arteries. The same could well be true in human patients, and treatment would consist of dietary strategies that slow or halt the process. - Nature, 26 May 2005

Adjusting the Circadian Clock

When we adjust to changes in our 24-hour clock, it isn’t a gradual process, according to research on rats. Instead, different components of the clock adjust at different speeds. A better understanding of the process could improve life for shift workers and transatlantic travelers alike. It is a particular problem for doctors and nurses alternating between day and night work. Researchers studied clock-resetting behavior in rats that were exposed to a six-hour delay of the light schedule, a shift that mimics a transition from New York to Paris or Chicago to London. By performing electrophysiological analysis of cells that constitute the central circadian clock, the researchers made a surprising discovery: one part of the clock mechanism exhibited oscillations in activity that corresponded to slow resetting of the clock, while another part of the clock exhibited a distinct pattern of activity that corresponded to fast resetting. The results show that, at least in rats, some brain cells adjust rapidly, while other parts are exposed to complex signaling patterns for about six days. - Current Biology, 24 May 2005

Gene Clue to Testicular Cancer

Researchers have located a gene that, when mutated or lost, causes testicular tumors in mice. They say their study offers insights into the genetic causes of the disease in humans because the cancer originates from the same cell type, the primordial germ cell, in both mice and men. The mutation causes a huge increase in testicular cancer incidence, from 5% to 94%. Although this dramatic rise was described in a mouse strain more than 30 years ago, it has taken until now for the gene to be identified. They have called the mutation Ter (for teratoma, a form of testicular cancer). - Nature, 19 May 2005

Anti-flu Compound in Red Grapes

Resveratrol, a chemical found in red grapes, blocks replication of the influenza virus in cell culture and in animals, researchers studying mice report. In cell culture experiments, resveratrol prevented influenza from replicating and it was therefore tried in mice. It had the greatest effect when administered three hours after exposure to influenza. Smaller but significant effects were seen when treatment began six hours after infection, but at nine hours after infection it had no effect. Pre-treatment also did not change susceptibility to infection. The treatment increased survival by 40% compared with placebo injections. The amount of virus present in the lung six days after infection was 98% lower in the resveratrol-treated mice. Resveratrol's anti-influenza activity seems to centre on its ability to interfere with key host-cell functions that are essential for virus replication. - Journal of Infectious Diseases, 15 May 2005

Search and Destroy Methods for Breast Cancer Cells

Ceramide, a naturally occurring substance that prevents the growth of cells, can be administered through the blood stream to target and kill cancer cells. When cancer cells die after chemotherapy or radiotherapy, it is ceramide that acts as executioner. By giving extra via intravenous injection, a study in mice suggests that we can provide a stronger cancer-killing therapy without additional side effects. Injected directly into the bloodstream, ceramide is toxic. It is also a fat, and therefore insoluble in water. But the scientists used nanotechnology and encapsulated the ceramide in tiny packets called liposomes. Once ceramide had been shown to kill cancer cells in a test rube, they tested it in mice by injecting the liposomes on alternate days. After three weeks, the treated mice had one-sixth of the cancer cells of the untreated mice. The next step is to explore how additional chemotherapeutic agents could be incorporated into the liposomes for a more lasting effect. - Clinical Cancer Research, 1 May 2005

Preventing Brain Damage after Diabetic Coma

A by-product of glucose could be key in preventing brain damage after patients with diabetes have severe insulin reactions – severe hypoglycemic attacks – that result in a coma. The standard treatment is to give the patient glucose, which restores consciousness but may not prevent brain damage and cognitive impairment. The research was done on rats, but the findings are so positive that a clinical trial in humans may follow soon. Pyruvate is a naturally occurring, non-toxic by-product of glucose that circulates through the brain and body at low concentrations. Previous research showed that when brain cells are deprived of pyruvate, they starve and die. In the current study hypoglycemic rats were given 100 times the normal blood level of pyruvate to see if it could penetrate the brain and effectively prevent brain damage. The rats' memory and learning abilities were tested in a maze test six weeks later. Researchers found the rats given pyruvate with glucose did well in memory and learning tests six weeks later, and tests showed they had 70-90% less brain damage than the rats given just glucose. This study sets the stage for future research on pyruvate as a treatment for hypoglycemia. - Diabetes, May 2005

Protein Crucial for Lyme-disease Bacterium

When the tick-borne bacterium that causes Lyme disease lacks a specific protein that responds to an incoming meal of blood, it cannot be transmitted from the tick to a new animal host, researchers have found. The findings, using mice, suggest that the protein, called BptA, is essential for the bacterium Borrelia burgdorfei (Bb) to survive in the gut of its tick host and may offer a potential new target for agents aimed at eradicating Lyme disease. When an infected tick bites an animal or a human, the bacteria are transmitted to the new host. Infection causes fever, malaise, fatigue, headache, muscle and joint aches, and a characteristic rash that surrounds the site of infection. In the study, researchers genetically altered the Bb bacterium to make a ‘knockout’ form that lacked a gene that codes for the protein BptA. Without the protein, bacteria were unable to utilize the blood on which the tick feeds when it bites a victim. The results required a comprehensive assessment of the total life cycle of the bacterium. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0502565102, 28 April 2005

Key Player in Inflammation Found

A protein called IKK alpha shuts down inflammation following an immune response to invading pathogens. In research with mice and lab cultures of immune cells called macrophages, scientists found that IKK alpha stops the inflammatory response before it can damage cells and organs. This discovery could help scientists find new ways to deal with autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and lupus, as well as drug-resistant bacterial infections and flesh-eating staph infections. For example, it may be possible to create an IKK alpha inhibitor that boosts the body's inflammatory response so it's better able to fight such infections. IKK alpha is part of a sophisticated two-pronged system that maintains a proper inflammatory response. It was already known that IKK alpha's sister protein, IKK beta, initiates the body's inflammatory response. However, little was known about the mechanism for halting inflammatory response before it injures tissue. - Nature, 28 April 2005

Exercise Slows Development of Alzheimer's

Physical activity appears to inhibit Alzheimer's-like brain changes in mice, slowing the development of a key feature of the disease. The research demonstrated that long-term physical activity enhanced the learning ability of mice and decreased the level of plaque-forming beta-amyloid protein fragments – a hallmark characteristic of Alzheimer's disease (AD) – in their brains. A number of population-based studies suggest that lifestyle interventions may help to slow the onset and progression of AD. Because of these studies, scientists are seeking to find out if and how physically or cognitively stimulating activity might delay the onset and progression of Alzheimer's disease. In this study, scientists have now shown in an animal model system that one simple behavioral intervention – exercise – could delay, or even prevent, development of AD-like pathology by decreasing beta-amyloid levels. Young mice genetically modified to develop AD were allowed to use running wheels. Mice that used the running wheels for five months took less time than the sedentary animals to find the escape platform. Mice that had exercised also had significantly fewer plaques and beta-amyloid fragments (peptides) in the brain. The mechanism underlying this difference began within the first month of exercise. - Journal of Neuroscience, 27 April 2005

Lab Animals Cured of Hemophilia

Newborn mice and dogs with hemophilia A have been restored to normal health through gene therapy developed by researchers. The technique introduced into the animals' cells a gene that makes clotting factor VIII, which is missing in 80% of human hemophilia cases. The animals produced about 20 times more factor than has been achieved in prior attempts using gene therapy for hemophilia A in dogs. In addition, the technique has the advantage of not prompting an immune response, which has often blocked the blood clotting activity of introduced factor VIII in hemophilic animals. Since treatment more than a year ago, the blood of the mice and dogs in this study has maintained a normal level of clotting factor activity, and the animals have had no incidents of bleeding. - Proceedings of the National Academy of Sciences, 26 April 2005

A Future Drug for Alzheimer’s?

Heparansulphate, a long sugar molecule needed for normal fetal development, is produced by most cells in the body. Using genetically modified mice, it has now been found that heparansulphate is necessary for presence of abnormal amyloid protein deposits in the body. These protein deposits appear in several serious diseases including Alzheimer’s, BSE, old-age diabetes, and amyloidosis.  Researchers used genetically altered mice that produce high quantities of the enzyme heparanase. This enzyme cuts the heparansulphate chain into short segments. Both the genetically altered and the normal control mice were stimulated with a treatment that usually leads to rapid build-up of amyloid in their internal organs. The modified mice proved to be completely resistant to amyloidosis of the liver and kidneys, unlike the control mice. The findings offer hope that short segments of sugar chains will be useful in drugs for Alzheimer's and other amyloid disorders in the future. - Proceedings of the National Academy of Sciences, 26 April 2005

Targeted Proteins May Treat West Nile Disease

Targeted proteins called monoclonal antibodies may work to treat West Nile virus, the mosquito-borne disease. Researchers found the laboratory-engineered antibodies cured mice infected with the virus, which usually causes only mild fever but can cause deadly brain inflammation in some patients. There is no proven therapy for people with serious West Nile disease. The researchers decided to develop monoclonal antibody after finding that antibodies taken from the blood of people who recovered from West Nile fever could cure mice infected with West Nile virus. They made 46 monoclonal antibodies and screened them until they found the most effective ones against West Nile virus. A humanized version of the most effective antibody protected mice bred to be susceptible to West Nile virus from death even if given after severe infection was established. - Nature Medicine, online DOI: 10.1038/nm1240, 24 April 2005

Making Mice Hibernate Offers Trauma Treatment

Scientists have induced a state close to suspended animation in a mammal for the first time, a long-sought achievement that could lead to a host of medical advances for people. By exposing mice to hydrogen sulphide gas, researchers managed to place the animals into a condition equivalent to hibernation, which could be rapidly reversed without apparently harming the creatures simply by letting them breathe fresh air. Slowing metabolic functions to a near standstill preserves organs and other tissues. That could, for example, give critically ill patients awaiting organ transplants more time, keep patients suffering severe blood loss from car accidents or gunshot wounds alive long enough to get transfusions and surgery, minimize damage from heart attacks and strokes, and help minimize the side effects of cancer chemotherapy and radiation. - Science, 22 April 2005

Brain Connections: Use Them or Lose Them

Neuronal competition helps connections to form in the brain: the branches of less active neurons are more likely to retract – and, it now seems, less likely to grow – than those of their more active neighbor, according to new research with zebrafish. - Nature, 21 April 2005

Anti-anxiety Circuit in the Brain

Researchers have discovered in mice how the brain responds to external stimuli that signal safety. Their findings could aid in treating psychiatric disorders involving a feeling of loss of safety, as well as understanding why some people respond badly to trauma while others do not. The work suggests that, in addition to the brain's well-known fear circuits, a second circuit exists and probably malfunctions in people with anxiety disorders. It opens up hope for other types of treatment that can act on your sense of safety and security. The safety circuit may also improve understanding of addiction since it operates in the some of the same areas of the brain thought to be involved in addiction, since people often experience a feeling of courage after taking them. In their experiments, the researchers conditioned mice to associate a particular sound with the knowledge that they were safe from danger (mild electrical shocks). They recorded the brain activity before and after hearing the sound and found the sound led to reduced activity in an area associated with motivation and reward, the caudoputamen. The researchers are planning studies using humans to determine whether the same circuits exist in people. - Neuron, 21 April 2005

Protective Enzyme Can Promote Heart Failure

Enzymes that make the gas nitric oxide (NO) not only protect the heart from damage due to high blood pressure or a heart attack, but also promote heart failure through overgrowth and enlargement of the muscle tissue. This study on mice is the first to suggest future therapies for heart failure using chemical cofactors that control the enzymes’ action. Nitric oxide’s extensive portfolio of natural effects includes the ability to expand coronary arteries thus improving blood flow, and to help regulate the strength of the heart’s contraction. But there is clearly a biological cost to this activity in some situations when the enzyme changes form. In several experiments, the researchers simulated heart overgrowth in groups of mice, bred with and without the gene for the most prominent of the NO-making enzymes called NOS3. This enzyme stops functioning normally when levels of its cofactor, called BH4, decrease. Mice treated with BH4 or lacking in NOS3 had less enlarged hearts. The researchers plan further experiments to evaluate the therapeutic effects of BH4 in hypertrophy and how it, together with NOS3, compensates for the damage that leads to heart failure. - Journal of Clinical Investigation, Online First DOI: 10.1172/JCI200521968, 14 April 2005

Nanoscale Particles Search and Destroy Breast Cancer

Researchers studying mice have developed a new approach to fighting cancer, based on nanoscale particles that can both detect and destroy cancerous cells. Current molecular imaging approaches detect cancer cells but don't offer a method of treatment, so the scientists developed an imaging and treatment method based on tiny spheres of silica coated with a thin layer of gold. These look for breast cancer biomarkers on cells surfaces, which then 'light up'. They have successfully tested the separate imaging and therapy aspects of the nanoshells in animals and are now evaluating the combined imaging/therapy nanoshells in a mouse tumor model, which they expect to complete by the end of 2005. - Nano letters, 13 April 2005

Brain Stem Cells Could Cure Diabetes

Scientists believe they could use brain stem cells to cure diabetes. Although the work is not yet ready to be tested on human patients, results in mice have been promising. Researchers were able to coax the immature brain cells to develop into the insulin-producing islet cells that are lacking in diabetes. Eventually, these could be used for curative transplants. Scientists have already been looking at using stem cells taken from embryos to treat diabetes. However, there have been concerns that these cells can turn cancerous, and they are difficult to work with in the laboratory. The latest research looked at whether stem cells taken from the brain might work just as well and avoid some of these issues. Islet cells resemble neurons and in some insects, such as fruit flies, the cells that produce insulin and regulate blood sugar are also neurons. The team transplanted brain stem cells into a cavity in the kidney in mice where other types of insulin-producing cells have been found to survive before. When the blood sugar went up in these mice, the transplanted stem cells released insulin. Four weeks later, the cells were still alive and producing insulin and none had turned cancerous. - Plos Medicine, April 2005

Mouse Clues to Dementia

Scientists have uncovered a clue about the causes of dementia in Huntington's disease by showing that mice susceptible to the disease have problems with learning and memory before the disease’s typical movement problems appear. The scientists also discovered that in Huntington's diseased brains, information processing between brain cells is disrupted, but the neurons do not die, which means the brain may respond to new anti-dementia drugs that can restore memory. The team trained normal and Huntington's disease-susceptible mice to perform a complex touch-dependent learning task. The healthy mice could improve on their performance and learn the task, but the mice with Huntington's disease could not, proving they had learning and memory problems. A second study showed that the Huntington's diseased brain lost its ability to change wiring patterns and suggested that the neurons were unable to reorganize themselves and strengthen their connections. Humans with Huntington's disease also have problems with touch perception. While more research is needed, Alzheimer's disease patients may also have defective nerve connections in the brain similar to Huntington's disease. If this is true, it might be possible to develop anti-dementia drugs that enhance information processing for both disorders. - Journal of Neuroscience, 23 March 2005

Cancer Treatments Prevent Inherited Glaucoma

High-dose radiation and bone marrow transfer treatments – of the type normally used to treat leukemia's and other cancers – has completely blocked the development of glaucoma in susceptible mice. The standard treatment for glaucoma is reducing the intraocular pressure by medication or surgery. However, it's increasingly clear that multiple mechanisms are at work in this disease. Mice with inherited glaucoma develop glaucoma in mid-life. Researchers treated these mice with a single, high dose of gamma radiation, together with bone marrow transfer. At 12-14 months - an age at which most of these mice have advanced glaucoma – the vast majority of mice did not have glaucoma. There was no detectable loss of the retinal ganglion cells, which typically degenerate in glaucoma. Full-body radiation and bone marrow transfer is not an appropriate therapy for human glaucoma and further research will determine the effectiveness of localized radiation to the optic nerve and retina. Ultimately, studies that reveal how the treatment works may lead to new types of therapy for people, and may even protect against other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. - Proceedings of the National Academy of Sciences, 22 March 2005

Tumor Warning in Blood Explained

Researchers have established a genetic mechanism in mice for the long-sought-after link between cancer and blood clotting disorders, a result that might point to therapies for certain invasive cancers. As early as 1865, doctors observed that certain blood clotting disorders serve as warning signs of so-called occult malignancies (which lack easily detectable symptoms), but the molecules underlying this link were unknown. Now scientists have found the human cancer-causing MET gene triggers both tumor development and blood clotting problems in mice. The team genetically engineered mice so that they could switch on MET expression in adult mouse liver cells. When they activated the gene, it triggered slowly progressing tumors, preceded by numerous blood clots in veins and fatal internal hemorrhages. MET boosts the levels of key enzymes involved in blood clotting. - Nature, 17 March 2005

Protective Molecule May Harden Arteries

A molecule that usually protects the body’s infection-fighting cells might also contribute to fatty build-ups that coat arteries and lead to heart disease. The molecule, called apoptosis inhibitor of macrophage or AIM, inhibits cell death in immune system cells called macrophages in mice. Macrophages circulate in the bloodstream and help the body fend off infection and foreign substances. The AIM-protected macrophages go on to encourage build-up of fats on the interior walls of arteries. The scientists exposed mice lacking AIM to a fatty diet that would normally induce atherosclerosis, hardening of the arteries. After several weeks, researchers found little to no atherosclerotic damage. But in mice that had normal AIM function, there was marked presence of plaque deposits in the arteries following a diet of high-fat food. This was dramatic evidence that showed suppressing AIM function translates into prevention of atherosclerosis. - Cell Metabolism, 15 March 2005

Missing Link Between Obesity and Diabetes?

Scientists are trying to determine how obesity and diabetes are linked, and what it takes to turn an obese person into a person with diabetes. New evidence in mice that may help explain that link - and may help them understand why some obese people never develop diabetes while many others do. The study suggests that the hormone leptin regulates blood sugar through two different brain-body pathways: one that controls appetite and fat storage, and another that tells the liver what to do with its glucose reserves. It's already known that disrupting leptin's appetite-controlling role leads to obesity, and that obesity is known to significantly raise the risk of diabetes. But the new result suggests it may take disruptions to both pathways to bring on full-blown diabetes and overwhelm the body's ability to control blood glucose levels via the action of insulin. - Cell Metabolism, 15 March 2005

New Clues to Cause of Iron Disorder

Researchers have identified a protein in mice they believe is key to the iron disorder hemochromatosis. The finding could lead to new treatments for this relatively common disease, in which tissues become overloaded with iron. About one in every 200 to 300 Americans are affected by hemochromatosis, which can lead to organ failure if left untreated. The study found that the protein ferroportin is the major, and possibly only, iron exporter functioning at key points of iron absorption and release in the body. This suggests that iron accumulation in people with hemochromatosis may be the result of ferroportin-related loss of control over iron export. The researchers disabled ferroportin in selected tissues and then system-wide in developing mice. Mice that completely lacked ferroportin died early in development, due to a failure of iron transfer from mother to embryo. Mice lacking ferroportin in all tissues except those critical for nutrient transfer from the mother survived, but quickly become anemic after birth due to a lack of iron in the blood. When the researchers examined the intestines, livers and spleens of these mice, they found an accumulation of iron within cells, indicating that the cells aren't able to release iron once it's absorbed. - Cell Metabolism, 15 March 2005

Gene Therapy Cures Inherited Liver Disease

A single dose of gene-virus combination cured rats of a inherited liver disease in which lack of a gene causes the accumulation of bilirubin – which, untreated, results in jaundice and brain damage. This is the first time this disease (Crigler-Najjar syndrome) has been completely cured long term with a single injection in an adult animal. Crigler-Najjar syndrome is currently treated by placing the person under special UV lights. It is an unwieldy and time-consuming treatment. The treatment used a specially developed adenovirus to carry the gene into the animal’s cells. This viral vector, as it is called, was manipulated so that it minimized toxic side effects. The viral vector itself is important because it has no long term effect. It does not become part of the genetic machinery of the cell and poses no risk of causing cancer. A one-time cure for all adults using this technique is unlikely, but it poses a real promise for long-term alleviations of the toxic symptoms of these kinds of diseases. The treatment could be repeated when needed. - Proceedings of the National Academy of Sciences, 15 March 2005

RNAi Meets MND

A genetic treatment called RNA interference might have therapeutic effects against motor neuron disease (MND or amyotrophic lateral sclerosis or Lou Gehrig disease). Hereditary forms of the disease are caused by mutations in a protein known as SOD1, and mice engineered to carry a copy of the human gene show symptoms similar to those in people with MND. Two teams showed that delivering small interfering RNAs that block the synthesis of SOD1 in these mice delays the onset of the disease and slows its progression. They then used gene therapy to replace a healthy copy of SOD1 instead. As treatment options for people with MND are limited, the results of these two groups open a new avenue to pursue in the fight against this debilitating disease. However, the work is in its infancy and much more research is needed ahead of human trials. the technique might also be useful in other diseases of the nervous system such as inherited forms of Parkinson’s disease or Huntington’s disease. - Nature Medicine, online, DOI: 10.1038/nm1205, 13 March 2005

Visualizing Alzheimer’s in the Living Brain

A hallmark of Alzheimer’s disease is the build-up of amyloid plaques (toxic protein clumps) in the brain, but these have only been detectable by examining brains after death. Now scientists using mice have developed a new technique for seeing amyloid plaques in living brains using MRI scanners, an important step towards developing an early diagnostic test. The scientists injected this substance called FSB into the brains of m