MS Multiple sclerosis (MS) is a debilitating neurological disorder which affects up to one in 7000 people. Damage to the white matter of the brain causes increasing physical and eventually mental disability. There is currently no cure, but a mouse engineered to mimic the disease could be about to give hope to sufferers. Although there are a number of theories as to the underlying cause of the disease, one of the main mechanisms is the breakdown of brain tissue by the body’s own immune system. The collagenase-2 protein has been implicated in this breakdown, because it can be responsible for breaking down the blood-brain barrier, which allows the errant immune cells into the brain. The researchers found that in mice engineered to lack collagenase-2, and in mice treated with a drug that blocked its effects, the progression of the disease was considerably lessened. The protein could be a future target for treatments in humans. - Journal of Biological Chemistry DOI: 10.1074/jbc.M709522200, 4 April 2008

Scientists working with deer mice appear to have confirmed what we’ve been told for years by our mothers; the best medicine for fighting a cold is to keep well-fed. The researchers found how differing diet regimes affect the production of B-cells in the mice. B-cells are the immune system’s primary way of regulating the activity of antibodies, and are therefore its ‘memory’ cells. In those animals that had their food intake decreased by a third, levels of B-cells were significantly lower. The explanation for this is likely to be that maintaining immune system uses a lot of energy, so at of the year when food is scarce the body responds by reducing its activity. The result is that the immune system is less able to ‘remember’ how it fought past infections, and must fight new ones afresh. The research could have important consequences for human medicine, as vaccinations rely on B-cell activity. Ensuring that vaccinated people, especially in developing counties, have a good diet may be just as important as getting the vaccine itself to them. - Physical and Biochemical Zoology DOI: 10.1086/587090, 1 April 2008

One of the mutations which makes cells cancerous – the disabling of genes involved in cell-death – also makes them particularly hard to kill. It becomes impossible to flick a genetic switch and persuade the tumors to die. But scientists working with mice may have found a way to do the next best thing – putting the tumors to sleep. The research team found that the Id1 gene is essential to the growth of some types of breast cancer. When they stimulated the gene in healthy cells, the scientists found that the mice developed tumors. These tumors, with their high Id1 expression, became very aggressive and spread to the rest of the body. When the scientists inhibited the action of Id1 in an already-established tumor, they found that it halted their growth - effectively freezing them. Once they couldn’t grow, the immune system was able to break them down. In light of this, scientists hope that Id1 will prove a good target for future therapies in humans. - Proceedings of the National Academy of Sciences, Early Edition DOI: pnas.0801505105, 31 March 2008

Liver cirrhosis is the progressive loss of liver function due to the severe scarring of liver tissue, and usually results from alcoholism or hepatitis infection. It is thought this scarring is irreversible, and can eventually lead to death; currently, the only effective cure is a liver transplant. But scientists working with mice now believe they may have developed a new treatment. Hepatic stellate cells – a type of liver cell - are responsible for the scarring, which occurs when they secrete collagen in response to damage. The experimental cure works by wrapping a molecule that blocks collagen production in a vitamin A coating. The hepatic stellate cells are programmed to absorb vitamin A, and therefore also take up the collagen-blocking molecule. Disguised by the coating, the compound successfully stops further cirrhosis, and the research team found that the liver could then regenerate itself to compensate for existing damage. They hope that a drug for use in humans will be developed within a few years. - Nature Biotechnology, Online DOI: 10.1038/nbt1396, 30 March 2008

Although it is an important tool in treating cancer, chemotherapy can have a debilitating effect upon its recipients, including muscle wasting, fatigue, and loss of appetite. Because of this, doctors recommend that patients eat before the treatment – but new research in mice could turn that advice on its head. Scientists found that when they administered the chemotherapy drug cyclophosphamide to mice with brain tumors, healthy cells as well as cancerous cells were killed, with only a fifth of the cells surviving the treatment. But when the mice were starved before being given the treatment, four in five healthy cells survived, while the cancerous cells were killed off at the same rate as before. The researchers believe this effect is due to the ability of normal cells to slow down their metabolism during starvation, thus protecting themselves from damage by chemotherapy. Cancer cells, on the other hand, turn off that machinery in order to divide uncontrollably, so feel the full effects of the drugs. Scientists have stressed that further tests must be done to establish the mechanism in humans. - Proceedings of the National Academy of Sciences, Early Edition DOI: 10.1073/pnas.0708100105, 30 March 2008

Thanks to new understanding of the disease in mice, a new treatment for cystic fibrosis (CF) may be on the cards. One of the leading causes of death in CF is repeated infection of the lungs by bacteria, which eventually cause so much damage that only a complete lung transplant can save the individual. The infections had previously been thought to occur due to the bacteria evading the immune system in the thick CF mucous. Now, scientists believe that the infections may actually be due to the inability of CF sufferers to break down ceramide, a type of fat. When ceramide builds up, it leads to cell-death and inflammation, thus creating the conditions for a bacterial infection to take a foothold. Scientists have found that when CF-mice are given a drug to block the production of ceramide, they have lower levels of the fat, which results in fewer infections and healthier mice. The scientists hope that an appropriate dose of the drugs will have a similar effect in humans, without blocking ceramide production completely. - Nature Medicine, Online DOI: 10.1038/nm1748, 30 March 2008

The modern obesity epidemic is often blamed on the human sweet tooth; we enjoy the taste of high-calorie food, and can’t get enough of it. But new research in genetically modified mice suggests that the predilection might go further than previously anticipated. The experimental mice had their trpm5 genes – without which they cannot taste sugar – knocked out, so were ‘sweet-blind’. They were then given the choice of two drinks; sugared water, or water with a low-calorie artificial sweetener dissolved in it. Despite not being able to taste any difference between the two, they developed a strong preference for the high-calorie sugared water. There seems to be another pathway, apart from taste, that acts as a reward mechanism for eating calorific food. If the findings are applicable to humans, they could have implications for weight-loss efforts – particularly if a way were found to block the reward pathway. - Neuron DOI: 10.1016/j.neuron.2008.01.032, 27 March 2008

As governments around the world continue to prepare for a possible outbreak of H5N1 bird flu in humans, we are still searching for an effective vaccine for the strain. Scientists hope this may be about to change after experiments in mice yielded promising results. The virus is made up of a number of different proteins, and these proteins are in turn composed of a variety of ‘domains’. One of the domains of the virus’ M2 protein is called the cytoplasmic tail. Previous research in a different influenza strain had shown that deleting this cytoplasmic tail resulted in a growth defect in the viruses, suggesting that it plays a vital role in replication. Scientists succeeded in mutating the same protein in the H5N1 virus, before vaccinating mice with the mutant virus. They found that when the vaccinated mice were then exposed to a lethal dose of normal H5N1, the virus could not replicate, and the mice fought off the infection. The hope is that this research could form the basis of a human vaccine against the ‘flu strain. - Journal of Virology DOI: 10.1128/JVI.01899-07, March 2008

Researchers have found a new way to encourage the growth of blood vessels in mice. The finding could help treat heart disease and cancer in future. The scientists found that when tissue is starved of oxygen, a molecule called PGC-1alpha senses the change and encourages the body to grow new blood vessels in the affected area to restore oxygen flow. It is already known that another molecular pathway, involving vascular endothelial growth factor (VEGF), can have a similar effect. But mice seem to need both pathways for the best response to oxygen starvation – GM mice lacking PGC-1alpha were less able to grow new blood vessels. A number of anticancer treatments work by stopping the growth of new blood vessels feeding the tumors. Until now, these therapies have focused on the VEGF pathway. The new study suggests that if such therapies also targeted PGC-1alpha, they might be more effective. - Nature DOI: 10.1038/nature06613, 21 February 2008

Brain cells grown from human embryonic stem cells can help repair brain damage in rats after a stroke. Researchers encouraged human embryonic stem cells to develop into neural stem cells. When these stem cells were transplanted into the rats, they grew into brain cells to replace those lost during the stroke. Some of the rats had lost the power of control in their limbs as a result of the stroke, but after treatment some of this control was recovered. The researchers think a similar technique could be used in patients within five years. - PLoS ONE DOI: 10.1371/journal.pone.0001644, 20 February 2008

Growing Beta Cells

Researchers have turned human embryonic stem cells into functioning pancreatic beta cells in mice, in a study that could help treat type-1 diabetics. Type-1 diabetics have no insulin-producing beta cells and cannot respond to changes in blood sugar. Scientists have considered turning embryonic stem cells into beta cells to treat diabetics, but they have had no success until now. Researchers treated embryonic stem cells with a chemical cocktail that encouraged them to become pancreatic endoderm cells, the cells present in the foetus that go on to form the pancreas. When these immature pancreatic cells were injected into the pancreas of diabetic mice, they developed into beta cells and began producing insulin. After two months, the beta cells were responding normally to rises in blood sugar after feeding. Tests in humans could begin as soon as safety considerations have been considered. - Nature Biotechnology DOI: 10.1038/nbt1393, 20 February 2008

Gene Therapy for Brain Cancer

Research with rats suggests that gene therapy could be used to treat glioblastoma multiforme, a common and fatal brain cancer. Researchers removed all of the dangerous genes from a virus and used it to deliver two key proteins directly to cancer cells in the brain. One of the proteins acts as a marker to encourage the body’s immune cells to attack the cancer cells. The other protein fights the cells from the inside – it becomes toxic inside the tumor and kills the cancer cells. Rats with the brain cancer had their condition reversed using the gene therapy. The researchers are now about to begin human trials using the therapy. - Molecular Therapy , 19 February 2008

Controlling the amount of nitric oxide in tumors could help improve the effectiveness of anti-cancer treatments, according to a study with mice. As tumors grow, new blood vessels develop to feed them with oxygen. But the new vessels are leaky, making them unsuitable for delivering chemotherapy drugs to the tumor. Drugs that suppress the growth of new blood vessels in tumors improve the effectiveness of chemotherapy drugs. Scientists think this is because the vessel growth-suppressing drugs encourage existing blood vessels to develop properly without leaks, making them more effective for delivering anti-cancer drugs. Blood vessel growth is controlled by nitric oxide, so restricting the amount of nitric oxide around a tumor could also encourage existing blood vessels to develop properly. When researchers modified cancer cells to produce less nitric oxide and injected the cells into mice, the tumors that developed were fed by well-developed blood vessels that were suitable for chemotherapy treatment. - Nature Medicine, online DOI: 10.1038/nm1730, 17 February 2008

First Chikungunya Animal Model

Researchers have created a mouse model for the chikungunya virus (CHIKV), a new virus that led to an epidemic in the Indian Ocean in 2005. The virus leads to fever, joint pains and a skin rash, but the factors responsible for the symptoms are unclear. The new model could help explain how the disease develops. Researchers deleted a gene for a protein that plays an important role in the mouse antiviral response. When one copy of the gene was deleted, the mice mimicked the benign form of CHIKV, but with both copies removed the mice mimicked the severe form of disease. Using the mouse model, the researchers have shown that CHIKV begins in the liver and then spreads to the joints and muscles. They expect the model to help in the search for an effective treatment. - PLoS Pathogens DOI: 10.1371/journal.ppat.0040029, 15 February 2008

Mice missing a gene could help in the identification of new treatments for bipolar disorder. Researchers discovered that mice missing the gene, NR-2E1, are prone to attack and kill other mice. Now they have found that the gene is also mutated in patients with bipolar disorder (formerly called manic depression). The gene seems to regulate the development of the front region of the brain, which is involved in decision-making. It suggests that bipolar disorder results from developmental problems. Next, researchers will take different varieties of NR-2E1 from patients and study their action in mice to see which lead to most aggressive behavior. - American Journal of Medical Genetics Part B DOI: 10.1002/ajmg.b.30696, 18 January 2008

Controlling the amount of cholesterol in the brain could help delay the onset of Alzheimer’s disease, according to research with mice. Researchers discovered the enzyme ABCA1 in 2001, and found that it controls the level of cholesterol in the blood. But it also seems to prevent the formation of the plaques that are common in the brains of Alzheimer’s patients. GM mice lacking the enzyme produce many more plaques than normal. Now, researchers have produced GM mice with high levels of ABCA1 in the brain. When these mice were bred with mice prone to Alzheimer’s, the offspring developed the disease at a slower rate than normal. Drugs to increase the level of ABCA1 could help treat Alzheimer’s. Such drugs already exist, but they also lead to unwanted fat build-up in the liver. - Journal of Clinical Investigation, online DOI: 10.1172/JCI33622, 17 January 2008

Research with mice suggests that melanoma arises because of a small population of cancer stem cells. Scientists know that the protein ABCB5 is found on the surface of some skin cells and helps skin cancers resist treatment. They thought that the protein could help identify cancer stem cells. The researchers took human melanoma cells and separated those cells producing the protein. When they injected these cells into mice, over half of the mice developed tumors. But when the researchers injected mice with the human melanoma cells lacking ABCB5, only one mouse of 23 developed a tumor. The study suggests that ABCB5 can act as a tool to identify – and ultimately eliminate – the dangerous cancer stem cells, which are capable of re-growing a tumor from scratch. - Nature DOI: 10.1038/nature06489, 17 January 2008

Researchers have identified a better method of alleviating chronic pain while avoiding side effects such as drowsiness, following a study with mice. The spinal cord helps to organize pain signals, and prevents many from reaching the brain through the action of a molecule called GABA. Medicines such as diazepam (valium) increase the activity of GABA, but they lead to addiction and drowsiness. Diazepam is an indiscriminate drug, say the researchers, because it interacts with four different GABA receptors. Now, research with mice suggests a therapy can be just as potent by targeting just two of those receptors. Researchers produced GM mice in which just two of the receptors could be targeted by drugs, and found that they could still alleviate pain in these mice. New medicines to target a narrower arrange of GABA receptors could avoid unwanted side effects. The next step is to identify the drugs that will work in humans. - Nature DOI: 10.1038/nature06493, 17 January 2008

Research with mice suggests that some probiotic bacteria in food can cause metabolic changes in the body and prevent weight gain. Scientists fed a group of mice on a solution containing one species of the bacteria found in yoghurt. A second group of mice was given a saline solution instead. After two weeks, both groups of mice still had very similar populations of gut microbes. But the metabolic profiles had changed. The mice receiving yoghurt bacteria produced less bile acid. Because bile acid normally helps emulsify fat, which helps the body absorb fat from food, the mice producing lower quantities of the acid were less efficient at absorbing fat, and so remained thin. The researchers are excited to find that it is possible to alter metabolism by making small changes to gut bacteria. - Molecular Systems Biology, online DOI: 10.1038/msb4100190,15 January 2008

Industrial air pollution can cause defects in sperm, research with mice suggests. Researchers reared one group of mice downwind of two steel mills and a busy main road. A second group was given filtered air. When the researchers studied the sperm of mice in both groups three weeks later, they found more physical damage, in the form of DNA strand breaks, in the mice breathing polluted air. After 16 weeks, the mice breathing polluted air produced sperm with 60% more DNA mutations than the mice breathing normal air. Air pollution is already linked to breathing difficulties, but this is one of the first studies to examine its effect on fertility. - Proceedings of the National Academy of Sciences, online DOI: 10.1073/pnas.0705896105, 14 January 2008

Hair to Heal Nerves

Research with mice suggests that human hair could hold the key to regenerating damaged nerves. Following nerve damage, it is difficult to get the broken ends of a nerve to grow back together again. To help the process, surgeons use nerve guidance conduits – microscopic tubes which they attach between damaged nerve ends that give the nerve a scaffolding to grow around. But the conduits work only over short distances, and nerve regeneration is a slow process. Now, researchers have extracted keratin protein from human hair and shown that, when the conduits are filled with the protein, nerve regeneration speeds up. Keratin acts on the Schwann cells that help in the healing process. When the researchers tried to repair damaged nerves in mice using keratin, they saw nerve re-growth in all cases. Given enough healing time, the researchers think that the nerve re-growth could help the mice recover full muscle control. - Biomaterials DOI: 10.1016/j.biomaterials.2007.08.023, 1 January 2008

Research has identified a drug therapy that could help treat Batten disease, a fatal childhood neurodegenerative disease. There are currently no treatments for the disease, and children gradually lose motor skills, sight and reasoning. Now, researchers have succeeded in reversing some of the symptoms of disease in mice. They already know that mice with the disease have unusually sensitive brain receptor cells in the cerebellum, a brain region involved in sense perception and motor control. They gave mice with the disease a chemical to dull the activity of the nerve receptors. The mice stopped deteriorating and began to improve their coo - Experimental Neurology DOI: 10.1016/j.expneurol.2007.09.012, January 2008