Gel May Help Heart Disease Patients

A gel made of compounds found naturally in the body could be used to grow new blood vessels, research on rats has shown. Blocked arteries and blood vessels are a main cause of coronary heart disease. Fats and cholesterol in the blood can accumulate in vessels resulting in a clot or blockage which reduces the flow of blood to the heart. Now researchers have developed a gel which can create new vessels, bypassing the blockage, and restoring the flow of blood around the body. The gel contains enzymes which help break down blood vessel tissue as well as a growth factor (VEGF) that helps build new ones. Rats injected with the gel to treat a blood clot in the leg had a full return to normal circulation within two weeks. Over time the gel broke down completely and was replaced with normal tissue. The researchers think the gel could also be used to treat type-1diabetes, in cases where patients are given an implant of islet cells from the pancreas. Here the gel would be used to enrich a specific site with blood, helping the insulin-producing islet cells to function. In the UK, more than 70,000 people die of coronary heart disease each year. The team hope their research will one day be able to help treat millions of patients worldwide. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0905447107, 31 Dec 09

A vaccine based on the one used to prevent rabies can be used to protect against the monkey form of HIV (SIV), a new study has found. One strain of the human form of the virus is thought to have originated from the SIV strain. Researchers can now protect monkeys against SIV and hope the finding will help develop a vaccine for AIDS. The vaccine contains the rabies virus in an attenuated form making it harmless and less virulent. Currently there are two ways of creating the vaccine, using a recombinant form of the rabies virus, where the genetic material of the virus is reorganized to produce a different function. Both approaches produced neutralizing antibodies and an increased white cell response in monkeys which increased protection. Researchers noted the response as a significant antibody reaction against SIV. Scientists believe the research is of benefit to monkeys and humans in protection against viruses and wish to study the vaccine further. - Vaccine, DOI: 10.1016/j.vaccine.2009.10.051, 11 Dec 09

Delivering genes to specific cells which cause the lung disease emphysema could be key to alleviating breathing difficulties, research on mice suggests. A genetically inherited type of emphysema known as Alpha-1 anti-trypsin deficiency is often caused by a mutation in the Alpha-1 anti-trypsin gene. This mutation affects young people, making them susceptible to emphysema at an early age. Cells called Alveolar Macrophage (AM) cells, found in the lungs, have also been identified as contributors to the disease. A team of researchers decided to study mice with this mutation and targeted AM cells for gene therapy. After one treatment, mice were able to express the Alpha-1 antitrypsin, which eased symptoms of emphysema. This improvement was sustained and the mice did not need repeated therapy. The AM cells which carried the therapeutic gene survived for a lifetime of two years. Emphysema is a lung condition which causes shortness of breath. Damage to the structure of the lungs occurs over a gradual period. As a result parts of the body do not receive enough oxygen, causing fatigue and weight loss. Smoking is one of the main causes of the disease in the UK. The research challenges the commonly held view of AM cells being short lived and therefore not relevant to gene therapy. The scientists would like to do more research and hope it will be useful for human treatments. - Journal of Clinical Investigation, DOI: 10.1172/JCI36666, 21 Dec 09

Patients who are unable to form blood clots could be aided by a newly designed blood cell, research on rats has found. Normally blood is able to clot effectively for small wounds. However, larger injuries such as those caused by car crashes and in the battlefield, can often overwhelm the body's clotting mechanism and cause hemorrhaging. Upon injury, platelets - a type of cell found in the blood - attach to the walls of the damaged area. They then stick to each other with the help of other clotting proteins to stop the body from losing anymore blood. In the past, severely injured patients such as war soldiers and cancer patients who have a particularly low platelet count due to their treatment have had to rely on platelet transfusions. However this can be problematic as the platelets expire after five days. Now, a group of scientists have been able to overcome this by using nanotechnology to produce artificial blood cells that can induce a clot. The specially built cells, referred to as RGD, are spherical and include a specific amino acid sequence that natural platelets recognize and stick to, causing a clot. Rats normally clot within four minutes but after an injection of RGD, the clotting time was reduced by 23%, sealing the wound faster. The team now aims to study this design in larger mammals such as pigs, and hope it could help with emergency treatments in humans in the future. - Science Translational Medicine, DOI: 10.1126, 16 Dec 09

High blood pressure may be linked to disruptions in the circadian body clocks, a study on mice suggests. A circadian clock is a 24 hour cyclical rhythm in the body through which biochemical processes take place. Many researchers observe this rhythm to better understand how it regulates the body on a daily, weekly, or yearly basis. Previously research has found that many genes build and control the circadian rhythm. Now, a study using mice shows a strong link between a gene involved in the body clock and high blood pressure. Researchers found mice with abnormally high blood pressure also had an unusual amount of the hormone aldosterone, which has a role in raising the water retention of the kidneys. Researchers were able to show the clock controls the gene which codes for aldosterone. The gene is similar to one found in humans. As a consequence of the erroneous gene, the hormone is produced in irregular amounts and raises blood pressure causing hypertension. Hypertension can lead to heart attack, stroke and kidney damage as well as many other serious conditions. The team would like to conduct further studies and hope that this finding will influence future ways of treating hypertension to prevent heart disease. - Nature Medicine, DOI: 10.1038/nm2061, 13 Dec 09

A new study has shown that the food sweetener fructose can cause dangerous body fat deposits and trigger diabetes and heart disease in humans. Initial research in rats showing the potential health problems of a diet rich in fructose have let to a new study in humans with worrying results. According to the findings, the commonly used food sweetener can lead to fatty deposits around internal organs and can contribute to obesity, diabetes and heart disease. Derived from corn, fructose is a sugar widely used in foods such as yogurts, cakes and fruit drinks. Naturally present in small amounts in fruit, it is also a cheaper substitute for another popular form of sweetener, glucose. However, unlike glucose, it cannot be broken down by the digestive system and often arrives intact at the liver. There, it interferes with natural digestion processes involved in burning and storing fat. Previous studies in rats found that consuming fructose led to insulin resistance, resulting in diabetes. There was also evidence showing signs of dyslipidemia, a condition where abnormally large quantities of fat are found within the body. Now, scientists have been able to support the earlier finding in rats with studies on humans. Over ten weeks, sixteen volunteers were given strict diet with high levels of fructose and were monitored. A second group were given high levels of glucose instead of fructose. The researchers found the group with fructose in their diet had produced new fat cells around vital organs such as the heart and liver. There were also early signs of processing abnormalities which may give rise to heart disease and diabetes. None of these changes were observed in the group on the glucose-rich diet. The research could help parents and consumers make better informed decisions about diet. - The Journal of Clinical Investigation, DOI: 10.1172/JCI37385, 13 Dec 09

Loneliness and stress are more likely to cause breast cancer, a study using rats suggests. A team studied the difference between isolated rats and rats living in a social group. They separated newborns from groups and found that isolated rats had a greater risk of developing tumors which were more deadly. The isolation causes the rats to produce a higher amount of the stress hormone, corticosterone. Receptors that recognize this hormone were found in the tumor, directly feeding it, highlighting the link between the two. Previous research has shown that stress can activate cancer inducing genes in humans. More research is needed to show whether these results are also seen in humans, however. Scientists think this finding may begin to explain why women in high crime neighborhoods seem to develop breast cancer earlier and why patients with psychiatric disorders have a shorter lifespan. They believe the results apply beyond breast cancer in explaining the effects of social networks in protecting health. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0910753106, 11 Dec 09

Targeting host molecules instead of the virus has proved successful in killing the Hepatitis C virus (HCV), research on chimpanzees has found. Targeting host molecules instead of the virus has produced success in killing the Hepatitis C virus (HCV) research on chimpanzees has found. HCV is dependent on a host molecule of RNA in order to survive. The RNA molecule, referred to as miR-122, is involved in the regulation of many genes in the body. Researchers think this molecule may help the virus in replication or disguising it from the immune system. To find out, a team of scientists conducted a trial in which they administered a special miR-122 blocking chemical to four HVC positive chimpanzees. Two of the chimpanzees were given a low dose of the blocking treatment, the others a high dose. The high dose resulted in an HCV reduction of 99.5%. What's more, the virus didn't develop any resistance to the medication. Approximately 170 million people worldwide are infected by HCV. The virus affects the liver and can lead to advanced scarring which may result in liver failure or cancer. Treatment combining two antiviral drugs is available providing a 50-80% eradication success rate. New medicines have been manufactured but the virus has been able to develop a resistance to them. This breakthrough could increase the effectiveness of current HCV treatments. However the researchers would like to see further research into the side effects of the new drug for its safety in human trials. - Science, DOI: 10.1126/science.1178178, 3 Dec 09

The inability to form a blood clot in a fetal blood vessel has been linked to heart failure in newborns, a study using mice has discovered. Every fetus has a short blood vessel called the ductus arteriosus which allows blood to bypass and protect the fetus's fluid filled lungs, and helps to strengthen the heart. Normally, the vessel closes just hours after birth with the help of platelets, parts of the blood which promote clotting. In some cases, however, the vessel fails to close, causing a condition known as patent ductus arteriosus. As a consequence there is an increased pressure in lung blood vessels which leads to irregular heart rhythms and eventually heart failure. A team examined the condition in mice, focusing on platelet function. They found that after birth platelets assemble in the blood vessel at the point of closure. In mice with defective platelet function this did not happen. As a result a similar condition occurred to that in humans involving an increase in blood to the lungs. The scientists also conducted a clinical trial with premature babies which showed that a shortage of blood platelets prevented the ductus arteriosus from closing properly. Researchers hope this breakthrough will lead to a change in current treatment methods. They suggest a transfusion of platelets for newborns to lower the risk of the condition. - Nature Medicine, DOI: 10.1038/nm.2060, 6 Dec 09

Vision in blind rats has been restored by a UK team in collaboration with international scientists.  A mutation occurring in rats genes can cause a defect in cells crucial to ensuring the eye functions properly. Retinal pigmented epithelial cells (RPE) provide a nourishing layer in the eye. As a result, this mutation causes photoreceptors - which are crucial to sight - to die, leading to blindness. Researchers used induced pluripotent stem cells - adult cells which can be reverted to a stem-cell like state and then turned into almost any type of cell in the body, to treat the condition in rats. They inserted the induced RPE cells into part of the eye before degeneration could occur. Rats with the inserted cells maintained their vision and could focus better on moving patterns than the rats that had not. The scientists hope that this discovery could lead to stem cell based therapies for age-related sight loss. - Stem Cells, DOI: 10.1002/stem.189, 3 Dec 09

A study involving mice has revealed that a hormone originating in the stomach has a new use in boosting resistance to Parkinson's disease. Ghrelin, the hormone produced in the stomach, circulates around the body. It helps in the stimulation of hunger, growth and learning. Recently it has been discovered to have roles in other illnesses such as the Prader-Willi syndrome and anorexia-nervosa. In Parkinson's disease, dopamine neurons cease to function properly. Consequently reduced quantities of dopamine, an important chemical in the communication of cells, are produced. The resulting symptoms include severe difficulty in walking, tremors, difficulty eating and delayed reactions. A team studied the role of ghrelin in mice and found it was protective of dopamine neurons. The hormone directly activates the brain's dopamine cells. Research showed mice deficient in ghrelin had a greater loss of dopamine cells than those that were not impaired. Results in mice could feasibly be translated to humans as ghrelin has the same role across many different species. In further studies, researchers would like to compare levels of ghrelin in healthy individuals and those affected by Parkinson's disease. Differing hormone levels could be a significant biomarker of the disease and its development. - Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.3890-09.2009, 25 Nov 09

Aggressive brain tumors can be killed and prevented from recurring using a virus, a new study using mice has found. The specially designed virus produces a protein called vasculostatin, stopping the growth of new tumor blood vessels. Research has proven that it is particularly effective against gliobastomas - deadly tumors which have high numbers of blood vessels. Researchers studied the effects of the virus on mice with human tumors under the skin and in the brain. They discovered that the mice affected with brain tumors and treated with the virus lived significantly longer on average than those without. One mouse remained tumor free for up to 120 days after the treatment, whereas there were no long term survivors in the control group. Brain tumors can be treated using a combination of methods involving drugs, radiotherapy, chemotherapy and surgery. Statistics show that less than a third of adults diagnosed with a brain tumor live for at least one year. After 5 years the survival rate drops to 14%. The study provides a potential new therapeutic strategy for fighting cancer, but further studies will be needed to understand how the virus works in combination with other treatments such as radiotherapy. - Molecular Therapy, DOI: 10.1038/mt.2009.232, 1 Dec 09

A cancer ‘vaccine' which can be implanted under the skin and instructs the body to attack tumor cells has proved successful in experiments with mice. Cancers often manage to survive in the body by evading the natural immune response. This new implant works by ‘reprogramming' the immune system to attack tumor cells more efficiently, in this case skin cancer cells responsible for melanoma. Conventionally, cancer vaccines work by removing cells from the body, treating them, and then reintroducing them. This can be inefficient, however, as the majority of re-injected cells will die before taking effect. This new technique, which takes the form of an implant the size of a fingernail, releases chemicals called cytokines which act as ‘recruiters' of dendritic cells - the messengers of the immune system. These in turn send signals to T-cells in the immune system which track down and attack tumor cells. Although other cancer vaccines are already in development, the researchers behind this study believe the new technology will be more efficient and less cumbersome than other vaccine treatments currently in clinical trials. Unlike chemotherapy, the system is specially designed to target tumor cells, so collateral damage to healthy cells is minimized. Other advantages of the vaccine are that it should offer permanent, body-wide resistance to cancer cells - thus minimizing the chances of relapse. - Science Translational Medicine, DOI: 10.1126/scitranslmed.3000359, 25 Nov 09

‘Friendly' bacteria living on the skin can be beneficial to our health, according to new research using mice and human cells. The skin's microflora - the bacteria that live on the skin - includes a common species, called Staphylococcus. Research has revealed that Staphylococci bacteria found on the skin's outer surface work to prevent inflammation, whilst causing an inflammatory response when they get inside a wound. The team used mice and human cells to investigate the mechanism behind this protective effect. They found that on the surface of the skin, the Staphylococci bacteria produce a molecule called lipoteichoic acid (LTA) which interacts with outer skin cells. The LTA cells appeared to dampen the skin's inflammation response, which can be useful in some instances, as prolonged inflammation can lead to skin diseases. The research not only provides a new example of how germs can actually be good for us, but suggests that antibacterial hand gels could exacerbate skin conditions such as eczema. It could also lead to new approaches for treating inflammatory skin conditions. - Nature Medicine, DOI: 10.1038/nm.2062, 23 Nov 09

Scientists know that the adult brain continues to create new nerve cells (neurons), but the reason why this happens is poorly understood. Now new research in rats and mice has brought this understanding one step closer. Researchers think that these neurons are involved with the removal of old memories so new ones can be created. Memories starting out in the Hippocampus, a memory holding part of the brain, eventually get transferred to the neocortex area, for permanent storage. A team of researchers therefore wanted to test whether the new neurons are involved in the process of transferring old memories into storage. The scientists studied mice with and without the ability to produce these new neurons. Using different stimulation chambers they assessed the memory the rats and mice retained in their brains over a period time. They found that the mice with the new neurons were able to transfer memories to the neocortex faster, allowing a greater space for new memories to be created and stored. Other researchers in the field of neurogenesis, feel that this is probably not the only role of the new neurons and suggest further research should be carried out. - Cell, DOI: 10.1016/j.cell.2009.10.020,13 Nov 09

Sheets of 'substitute skin' from human embryonic stem cells have been grafted onto mice in the laboratory. This is a first and could lead to the development of multiple cell lines to provide immediate treatment for burns patients. In the case of severe burns, patients are able to have the damaged tissue replaced with skin grown from their own cells. However, this process takes up to three weeks, which can put patients at risk of dehydration and infection until the graft is ready. Occasionally skin from dead bodies is used as a temporary covering, but this is far from ideal as its availability is limited and it could be rejected by the immune system. The team began by converting embryonic stem cells into skin cells. They then seeded the cells onto a special matrix which acted like an artificial scaffold. The resulting skin was grafted onto five mice, and after 12 weeks the layers had developed a structure similar to human skin. Although these mice had the advantage of no immune defenses to reject the human cells, the new technology could offer a temporary solution to human burn patients while the patients own cells can be grown. The team will now look into the possibility of using multiple lines of embryonic stem cells with various immune characteristics, to provide temporary skin suitable for a wide range of patients - The Lancet, DOI: 10.1016/S0140-6736(09)61496-3, 21 Nov 09

Researchers have made a step forward in treating nerve cells damaged in spinal cord injuries, using guinea pig tissues. Nerve cells are covered in a thick insulating layer called myelin. Very much like the insulation around electrical wires, myelin enables signals to be transmitted down the nerve without short circuiting. There are small gaps in the myelin layer where potassium channels are exposed which allows the impulse to do a kind of frog hop along the neuron, carrying the signal down the length of the cell. The researchers subjected guinea pig spinal cord tissue to stresses that mimic a compression injury of the spinal cord. Using imaging techniques, they saw that when the nerve becomes damaged, the protective myelin layer recedes, and potassium channels are exposed throughout the length of the nerve fiber. When the nerve cells are damaged in this way, they can no longer transmit impulses accurately or efficiently. Depending on how severe the myelin damage is, the result can be impairment, or total loss, of function of the nerve. Spinal cord injuries share many features with multiple sclerosis (MS). The team therefore took a derivative of the MS medicine fampridine and tested it on damaged guinea pig spinal cord tissue. The treatment restored function to the neurons, which were then able to successfully transmit signals. The researchers discovered that this is because the derivative is a potassium channel blocker, which prevents the leaking of electrical current and enhances nerve conduction. Fampridine has the disadvantage that it makes the nerve 'groggy' by increasing the time between nerve pulses. Its derivative did not have this effect, and was about 10 times more potent than the parent drug, reducing the likelihood of side effects. The compound will now be tested in live animals, and for use in MS as an alternative to fampridine. - Journal of Neurophysiology, DOI: 10.1152/jn.00154.2009, 18 Nov 09

A new method to treat arthritis has proven successful in mice, and holds strong hopes for treating other autoimmune disorders. Autoimmune diseases such as rheumatoid arthritis and diabetes occur when the body's immune system mistakes healthy tissue for foreign matter and destroys it. Cells called regulatory T cells (T-regs) can suppress a wide range of immune cells, making them an ideal candidate for the treatment of autoimmunity. However, these cells are rare and in limited supply. Dampening the immune system is also dangerous, as it leaves the body more susceptible to infections and other diseases. Therefore one of the key features of a treatment involving T-regs must be targeted delivery, ensuring damage to healthy tissues is minimized. Now, researchers have found a way of using much more common ordinary T-cells from mice by converting them into the rarer T-regs, then using these cells to treat arthritis. A virus is used to insert two genes into the T cells: one gene transforms the them into T-regs whilst the other introduces a receptor for a substance called ovalbumin, which ensures targeted delivery. Ovalbumin - a protein found in egg whites - was injected into the inflamed joints of arthritic mice so that when the modified T-reg cells were administered to the mice they only targeted the damaged tissues. The treatment successfully reduced the number of inflammatory cells in the mice, and decreased bone destruction. The artificially produced T-reg cells are much more stable than those that occur naturally, and are attracted to areas of the body where ovalbumin has been administered. This reduces the possibility that the cells could revert to T-cells and cause damage elsewhere. The researchers are confident that similar T-reg therapies could be developed to target autoimmune diseases that affect other parts of the body by using different receptors. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0907396106, 29 Sep 09

Researchers have discovered a new medicine which is able to stop lung tumors from growing in mice, even eliminating them altogether in half of all cases. The cancers being studied are specifically small cell lung cancer tumors. These grow and spread quickly rendering surgery unsuitable. Chemotherapy and radiotherapy initially work well at shrinking the tumors, but they usually grow back and become resistant to the treatment. Previous research had identified that the rapid growth and spread of small cell lung tumors is fueled by a growth hormone called FGF-2. The team was therefore looking for a chemical that would reduce the effect of this hormone. After laboratory tests on cells taken from human tumors, the researchers discovered that an inhibitor called PD173074 blocks the FGF-2 receptor, making the hormone unable to take effect. The team then tested the inhibitor in mice, using two different types of human small cell lung cancer tumors. The study looked at the inhibitor on its own and also in conjunction with cisplatin (a standard chemotherapy agent). In the first group of mice, the inhibitor on its own killed off tumors in half of the mice, which went on to remain disease-free for at least one year. In the second group, each of the medications alone slowed tumor growth, but when the medications were combined the tumor growth slowed down significantly faster than when a single treatment was used. The authors are planning to take the treatment, or a similar agent that targets the same hormone, into clinical trials next year. One of the benefits of this medicine is that it could be taken orally, as opposed to other chemotherapy treatments that are administered intravenously, which involves a hospital visit. - Cancer Research, DOI: 10.1158/0008-5472.CAN-09-1576, 10 Nov 09

Using outside-the-body gene therapy in pig and human lungs, researchers have repaired donated organs that were deemed too damaged to transplant. Many lungs harvested from donors are unsuitable for transplant as they are inflamed, which causes poor gas exchange. The new technique involves preserving the lungs at body temperature in a specialized chamber before a solution of oxygen, proteins and nutrients is pumped over the damaged tissues. The common cold virus (adenovirus) is then used to transport a gene which codes for the protein interleukin-10 (IL-10) into the lung tissue. Because IL-10 is a known anti-inflammatory the team hoped it would reduce the damaging inflammation in the lungs. In pig lungs, the team saw that the gene-treated lungs showed less inflammation and improved function after transplantation into recipient pigs. Tests on 10 human lungs unsuitable for transplantation also showed significant improvement in function. Researchers hope that the technique could also help to protect against post-transplant inflammation, and could also be used to repair other transplant organs such as kidneys and hearts. - Science Translational Medicine, DOI: http://dx.doi.org/10.1016/10.1126/scitranslmed.3000266, 28 Oct 09

Researchers have long known that overweight people are more likely to develop conditions such as diabetes and heart disease. In a new study researchers have uncovered evidence to explain how saturated fatty acids can lead to these chronic diseases. Some fatty acids look like bacterial invaders, so the body mounts an immune response to them, causing inflammation. It is thought that this inflammation is the cause of the chronic conditions associated with obesity. The researchers determined that a protein called TLR4 was key in causing this inflammatory response. Located on immune cells called macrophages, the protein recognizes invaders and controls the further release of macrophages. The team used chemicals to destroy the macrophages in the bone marrow of a group of mice and then injected them with new macrophages that had been engineered without the TLR4 protein. The team took the modified mice and normal mice, and fed them a high-fat diet. All the mice grew obese, but the mice without the TLR4 protein showed no sign of inflammation, and insulin levels were normal. The team is currently looking for medicines that block TLR4, with the hope that one day it may be possible to take medication to dodge the adverse health effects of being overweight. - Cell Metabolism, DOI: doi.org/10.1016/j.cmet.2009.09.006, 4 Nov 09

Past research has suggested that high protein diets, such as the Atkin's diet, can increase the risk of heart disease and kidney problems. However, a new mouse study has found that eating too much protein could also shrink the brain and cause Alzheimer's. Researchers used mice specially bred to develop Alzheimer's and fed them a number of diets. Some received a normal mouse diet; others a high-fat, low-carbohydrate diet; a high-protein, low-carb version (Atkin's); or a high-carb, low-fat option. They then measured the brain sizes of the mice, and the levels of plaques associated with Alzheimer's. Results showed that those with a high-protein, low-carb diet had smaller brains, with a less developed hippocampus (the area of the brain responsible for memory). They also saw that there were raised levels of plaque proteins in the mice receiving the high-fat low-carb diet, but with no outward signs or symptoms. Whilst this does not prove that high protein diets lead directly to Alzheimer's, raised levels of plaques in the brain are a strong link with the disease. The research seems to indicate that a balanced diet, with no one food group dominating over the others, is best for overall health. - Molecular Neurodegeneration, DOI: 10.1186/1750-1326-4-40, 21 Oct 09

Scientists have developed a new gene therapy successful in treating the most severe type of muscular dystrophy in mice. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease which causes progressive wasting and paralysis from an early age. There is no cure, and usually kills patients by their early 20s. DMD is caused by a genetic error in the gene for dystrophin, an important protein in muscle tissues. The new treatment, known as peptide-conjugated morpholino oligomer (PPMO), causes cells to skip a section of the mutated gene when producing the dystrophin protein. This results in a shorter protein with a different structure to the normal dystrophin protein. But the shortened protein is more functional than the original mutated form.   The idea is that this treatment will not be able to cure DMD, but will limit the effects of the condition making it a less severe disease. The therapy also contains a chemical marker to allow it to be easily absorbed by muscle tissue. This type of targeted delivery has always been a problem in past therapies for DMD. The team took knockout mice which exhibit similar symptoms to DMD patients as they lack the dystrophin gene along with another important muscle gene, utrophin. After treatment with PPMO, the mice showed improved mobility and prolonged live spans compared to those mice that didn't receive the therapy. There is currently a similar treatment in clinical trials, but it doesn't include a chemical marker to help absorption into the muscles. The researchers believe this therapy could move into clinical trials fairly soon. - Molecular Therapy, DOI: 10.1038/mt.2009.248, 20 Oct 09

Scientists have grown a thin strip of heart muscle, which is able to beat spontaneously, using stem cells from a mouse embryo. Currently there are many treatments to prevent a heart attack. However, after a heart attack there is no way to restore the damaged heart muscle. So far stem cells found in bone marrow have been used in an attempt to kick start stem cells within the heart to grow new cardiac muscle, but this approach has as yet proved unsuccessful. The new study took a more direct approach. The researchers discovered that master heart stem cells were present in both human and mouse embryos. They then engineered mice so that certain cells within the developing heart would glow fluorescent red or green. When tracking the fluorescence in the developing embryos, the researchers noted the areas where the two colors overlapped. These areas were where the cells responsible for developing heart ventricle muscle were located. The team seeded special scaffolding with these ventricle stem cells and managed to grow a thin strip of mouse heart muscle. Amazingly this muscle strip also spontaneously beat, just like a normal heart tissue strip. The team are trying to grow thicker, usable portions of muscle. They will also attempt to pinpoint the stem cells that develop blood supply to the heart, so that the new tissue will grow an essential blood supply. - Science, DOI: 10.1126/science.1177350, 16 Oct 09

Researchers have used gene therapy to correct movement problems in macaque monkeys with Parkinson’s symptoms. The problem with current treatments for Parkinson’s disease is that the drugs lose effectiveness over time, and can cause serious side effects. The team used a virus to introduce three genes into the brains of monkeys with a form of Parkinson's. These genes are involved in the production of dopamine, a neurotransmitter responsible for controlling movement and the brain’s motor system. The three genes have been introduced into animals separately in the past, but never together. Using specially designed probes to measure the dopamine levels in the brain, the team monitored the monkeys for up to three and a half years. Dopamine levels were restored to about half normal concentrations in the brain and the monkeys showed improved movement problems without any severe adverse side effects. It is stressed that this therapy is only a treatment, not a cure, as it only targets one of the symptoms of Parkinson’s disease – the tremor and movement problems. But after this successful trial an early stage human clinical trial using this technique is underway. Once researchers find the optimal dose, they plan to move to larger phase II trials. - Science Translational Medicine, DOI: 10.1126/scitranslmed.3000130, 14 Oct 09

In a mouse study, scientists have engineered stem cells to enhance their healing properties. Stem cells are already known to have the potential to repair most tissues in the body. However, the rate of repair is limited by blood supply, because blood provides the nutrients to the new tissue. Stem cells cannot always encourage enough blood vessel growth, so the team added an extra gene (for the protein VEGF) to the cells. VEGF is known to promote the formation of blood vessels. Scientists tested the effectiveness of these engineered stem cells using mice with injuries to their hind limbs. They saw that the mice which had received the modified stem cells had three times the number of blood vessels around the tissue compared to control mice. After four weeks, just one fifth of the mice had lost limbs, whereas nearly two thirds of control mice had required limb amputation. These results highlight a promising therapy for tissue repair after injury. The technique itself could also be applied to a number of disorders; different genes could be added to the stem cells to tailor them to carry out specific jobs. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0905432106, 5 Oct 09

Researchers have discovered that a derivative of cholesterol is necessary for forming brain cells. The researchers studied the development of dopamine-producing (DA) neurons in the brains of mice. They saw that the process is dependent on the activation of a brain receptor by oxysterol, an oxidized form of cholesterol.  The team genetically engineered mice embryos to delete two oxysterol receptors. The resulting mice had reduced DA neurons at birth, but when the team activated the receptors with oxysterol the neurons grew. The researchers also found that human embryonic stem cells form more dopamine producing nerve cells if they are treated with oxysterol in laboratory cultures. The treatment also reduced the tendency for the stem cells to show uncontrolled growth, which is often a problem with culturing stem cells in the laboratory. DA nerve cells are important in many brain functions, and are the cell type affected by Parkinson’s disease. It is therefore hoped that this discovery will make it possible to one day develop treatments to replace dead cells in the brains of Parkinson’s disease patients. - Cell Stem Cell, DOI: 10.1016/j.stem.2009.09.001, 2 Oct 09

A discovery in pigs could increase the number of transplants that can be performed. Researchers have developed a cocktail of drugs that doubles the time a donated heart is viable for transplant.  The team studied pig hearts and their deterioration once outside the donors’ bodies and on their way to the recipient. They pinpointed what caused the deterioration, and found there were already drugs on the market that could block the process. The cocktail of drugs both dilate the blood vessels and block channels in the heart. This prevents the heart from going into a type of ‘hibernation’ once it is starved of oxygen and nutrients. Following successful trials in rodents, the team tested the technique using pigs. They saw that the new solution could more than double the time the donor heart remained viable. Clinical trials of the new solution are expected to begin within a year, and there are also plans to adapt the technique to other organs such as the liver and pancreas. - American Journal of Transplantation, DOI: 10.1111/j.1600-6143.2009.02736.x, 1 Sep 09

Scientists have extended the lifespan of mice by manipulating their genomes. The team found that by genetically blocking the production of a protein called S6 Kinase 1 (S6K1) in mice, they could extend their lifespan by up to a fifth. These findings center around previous research, which has shown that a reduction in calorie intake by around a third for rats, mice, and primates, can extend their lifespan by up to 40%. S6K1 is involved in the body’s response to changes in food intake, therefore by blocking S6K1 the researchers found they could achieve similar results to calorie restriction, without reducing food intake. Genetically altered female mice lived for a total of 950 days, over 160 days (or one fifth) longer than their normal counterparts. At age 600 days (the equivalent of middle age in humans), they were leaner, had stronger bones, demonstrated better senses and cognition, performed better at motor tasks, and were protected from type 2 diabetes. Male mice showed little difference in lifespan, but demonstrated some of the health benefits, including less resistance to insulin. From research that began in worm models, studies such as this one in mice have provided targets for drug therapy. The next step is to test drugs involved in this process to see if they can slow the aging process. - Science, DOI: 10.1126/science.1177221, 2 Oct 09

Scientists have shown that the drug vorinostat is able to cross the blood-brain barrier, and reduce the development of brain tumors in mice. Breast cancer survival rates have been increasing over recent years with the development of drugs such as Tamoxifen and Herceptin, however the incidence of the cancer spreading to the brain is also increasing. The problem with brain metastases (tumors) is that drugs must pass through the blood-brain barrier in order to reach the tumor. The blood-brain barrier is a structure of blood capillaries in the brain with a largely protective role, ensuring that molecules such as viruses and bacteria do not reach the brain. However, this means that treating brain metastasis is difficult, as many drugs cannot penetrate the barrier. This is the reason that estimated survival one-year after the diagnosis of brain metastasis in breast cancer patients is about twenty per cent. The drug vorinostat has been found to slow the growth of several different types of cancer tumors in mice, and it has been approved in the US for human use against one cancer type (T-cell lymphoma). Previous studies had suggested that it could pass across the blood-brain barrier. Therefore researchers used a mouse model of human breast cancer, where the cells migrated to the brain, forming metastases. They then administered vorinostat to the mice, and saw high levels of absorption into the brain. Tests also showed higher levels of the drug in the metastases compared to the surrounding tissue. Overall, the development of large metastatic tumors was reduced by around two-thirds in the mice, compared to controls. This effect was linked to the ability of vorinostat to break DNA strands, and lower the effect of a DNA repair gene. Consequently the DNA would remain damaged, reducing the rate of tumor cell metastasis. Previous work by these researchers showed that vorinostat could enhance the effect of radiation therapy in mice with brain cancer metastasis, by enhancing the sensitivity of cancer cells to the damaging effect of radiation. Both of these studies mean that researchers are looking to begin clinical trials in humans in the future. - Clinical Cancer Research, DOI: 10.1158/1078-0432.CCR-09-1039, 1Oct 09

Studies using mice suggest that lack of sleep could increase the development of plaques in the brain, accelerating the development of Alzheimer’s disease. It is thought that the build up of toxic plaques in the brain causes Alzheimer’s disease by ‘clogging up’ information pathways. A protein called beta-amyloid is known to cause these plaques to form. A team of scientists looked at the effect of sleep on the levels of beta-amyloid in mice and humans. When mice were deprived of sleep, the levels of beta-amyloid increased by one quarter, and the plaque levels also increased. Further tests involving the administration of an insomnia drug showed that excess sleep can result in a reduction in the levels of beta-amyloid by over three quarters. Tests on 10 healthy men showed reduced levels of beta-amyloid in the cerebrospinal fluid at night, suggesting that the same mechanism is present in humans. - Science, DOI: DOI: 10.1126/science.1180962a, 24 Sep 09

After more than 50 experiments in mice, scientists have mapped out how a set of white blood cells (lymphocytes) set the pace of recovery after serious lung injury. In acute lung injury (ALI), inflammation in the lungs makes breathing difficult. This results in a lack of oxygen to the body. Previous research indicated that lymphocytes play a role in lung inflammation, so the researchers bred mice genetically modified to be lymphocyte deficient. They then exposed normal mice and the lymphocyte deficient mice to a gas containing bacteria known to cause injury to the lungs. They compared the death rates between the two groups of mice and saw a higher death rate in the mice without lymphocytes. They concluded that lymphocytes are key to recovery after lung injury. To determine which type of lymphocytes were responsible for this response, the team then injected mice with different types and combinations of lymphocytes. They found that the levels of a particular subset of lymphocytes known as Tregs were directly proportional to the levels of lung inflammation. To test the ability of Tregs as a potential therapy, they doubled the exposure of the bacterial toxin to the mice. This increased the death rate to half in untreated mice. However, when mice were administered Tregs after exposure to the toxin, the death rate fell to just one tenth, with many showing signs of recovery after just six days. Studies on lung tissue extracts from two people with ALI also showed that after 48 hours, Tregs were at 10 times the normal level. This discovery opens up the possibility of speeding up, or supplementing the levels of Tregs, so the next step is to identify the process by which Tregs cause the mouse immune response to repair the tissue. - Journal of clinical Investigation, DOI: doi:10.1172/JCI36498, 21 Sep 09

Researchers have identified the master gene that causes blood stem cells to turn into natural killer (NK) immune cells. NK cells are white blood cells, and are the immune system’s frontline defense against tumors, bacterial infections and viruses. It is thought that malfunctioning NK cells are involved in autoimmune diseases such as diabetes, where the immune system attacks healthy cells. The researchers ‘knocked out’ the E4bp4 gene in mice and saw that the mice produced no NK cells. The rest of the blood cells were unaffected and were at normal levels. As well as proving the role of E4bp4 in NK cell production, the ‘knockout’ mouse will provide scientists with an animal model that completely lacks NK cells. This model will help researchers to discover if NK cell malfunction is behind conditions such as autoimmune diseases and graft rejection. The team are also hoping to develop therapies to increase the number of NK cells. They hope that raised levels of NK cells would increase the chances of the body fighting tumors. Currently donor NK cells are used in cancer therapy, however due to donor-patient incompatibility they only have limited effectiveness. This method would eliminate this problem, as the extra cells would be produced by the patients themselves. - Nature immunology, DOI: doi:10.1038/ni.1787, 13 Sep 09

A new study identifies a stem cell that may cause some types of prostate cancer, at least in mice. Called CARNs (castrion-resistant Nkx2.1-expressing cells), they are responsible for creating luminal cells, which secrete chemicals into the prostate. When they inactivated certain tumor suppressor genes in the CARN cells of the mice, the team saw out-of-control growth of the luminal cells, which can lead to the formation of a tumor. The study also found that the cells did not rely on male sex hormones such as androgens to thrive. This is surprising as it is these hormones that control normal prostate growth. However, it would explain why prostate cancer often becomes resistant over time to drug therapies targeted at androgen production. Further studies will be needed of the exact mechanisms by which mutations can lead to unregulated growth of luminal cells, and why the tumors are not controlled by androgens. However, the study gives further insight into the mechanisms behind prostate cancer, and could lead to better-targeted therapies in future. - Nature, DOI: 10.1038/nature08361, 9 Sep 09

Researchers have discovered one reason why broccoli and other green leafy vegetables are definitely good for you. Using mice, they discovered that a chemical found in these green vegetables – sulforaphane – could protect arteries from clogging, so reducing the chance of heart attacks. Previous research has shown that certain areas of the arteries such as bends and branches are more prone to the build up of fatty plaques. The mouse study showed that, in these areas, a protein called Nrf2 is inactive. Responsible for breaking down clots, the lack of Nrf2 is one of the reasons why these areas are more vulnerable, so the team looked for a compound that would switch the protein back on. Sulforaphane was able to switch on Nrf2, and so boost the body's natural defense mechanisms against plaque build up in the mice. The team are now testing the effects of the vegetable form of sulforaphane, and they are confident that there is a strong argument for producing it as a pill. - Arteriosclerosis Thrombosis and Vascular Biology, DOI: 10.1161/ATVBAHA.109.193375, 4 Sep 09

New findings indicate that the link between diesel exhaust fumes and cancer lies in the ability of particles within the exhaust fumes to cause the growth of new blood vessels, which can aid tumor development. The study investigated the impact of diesel exhaust fumes on groups of mice. The first group had an implant designed to mimic the normal conditions in the body for cell growth. In the other, the blood flow to the hind limbs was reduced, to create an area with little or no oxygen supply. During the study, the mice were exposed to either exhaust fumes or filtered outdoor air for six hours per day, five days a week. For the rest of the time, they breathed filtered air. The level of exhaust particles mimicked levels found in urban areas. The team reported a six-fold increase in the formation of new blood vessels in the implanted tissues and aortas of mice exposed to the diesel fumes. In the mice with reduced blood supply, they saw a four-fold increase in new vessels to the hind limbs. The formation of new blood vessels is strongly associated with tumor growth; tumors grow rapidly, consuming large quantities of oxygen and nutrients. Further tests revealed that the increased growth of new blood vessels was due to activation of biochemical pathways. In addition, in tissues exposed to the exhaust fumes there was low-grade inflammation, which is often associated with tumor development, and reduced activity of an enzyme responsible for producing tumor suppressing substances. Whilst these results indicate that diesel fumes could increase the risk of cancer development and tumor growth, the results only show that the fumes promote the growth of blood vessels. Further studies will assess the effect of exhaust particles directly on tumor development. - Toxicology Letters, DOI: 10.1016/j.toxlet.2009.08.006, 2 Sep 09

It is well known that obesity can lead to health problems such as diabetes and cardiovascular disease, and it is thought that this is due to low-grade inflammation. Scientists believe they may have found the protein which causes this inflammation using mice. The protein, called angiopoietin-like protein 2 (Angptl2), is a fat-derived protein. The team showed that the levels of Angptl2 are raised in the fatty tissue of mice, especially in tissue with a low oxygen supply. Obese fatty tissue typically has poor oxygen supply, as there are fewer blood vessels supplying blood. They also showed that higher Angptl2 levels are found in the blood of people with higher body mass index and insulin levels. To test the effects of the protein directly, they bred obese mice lacking the protein. Results showed there was less inflammation in the fat tissue, and less insulin resistance. Other mice, of normal body weight, were bred to over-produce the Angptl2 protein. This group of mice developed inflammation and insulin resistance. Further tests showed that the protein triggers an inflammatory cascade, causing blood vessels to remodel and attracting immune cells. This then causes the inflammation which can lead to some of the health problems associated with being obese. This study identifies Angptl2 as a new molecular target that could have uses in the diagnosis and treatment of obesity and related diseases. - Cell Metabolism, DOI: 10.1016/j.cmet.2009.08.003, 2 Sep 09

Scientists have produced four infant monkeys using a technique which could stop women with genetic diseases passing them on to their children. Faulty DNA contained within cell structures called mitochondria was replaced by healthy mitochondrial DNA (mDNA) from a donor egg, so the faults were not passed from mother to baby. Defects in mitochondria affect one in 200 births and are serious for about one in 6,500 births. The new technique – called spindle transfer – has the potential to eradicate types of fatal liver failure, blindness, diabetes and deafness, as well as a type of muscular dystrophy called mitochondrial myopathy which currently affects about 3,500 people in the UK. mDNA also plays a role in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's. DNA is mainly confined to two structures within cells – the nucleus and the mitochondria. Mitochondria are the powerhouses of cells, converting food into energy that the body can use. The mDNA contained within them comprises less than 1% of all the DNA in the body and affects how cells convert food into energy. All the other genes that determine our characteristics are located within the nucleus. mDNA is passed from mother to child by egg cells; sperm cells do not transmit mDNA. The team took egg cells from macaque mothers and from donor macaques. They then removed the nuclei from both sets of eggs, transplanting the mother's nucleus into the donor egg. They then fertilized the eggs using IVF technology, and transplanted them into surrogate monkeys. The technique resulted in four healthy babies, including a set of twins. Because spindle transfer does not involve moving the mitochondria, which are incredibly delicate and prone to damage, scientists believe that the move from animal to human trials could happen within two to three years, although the health of the baby macaques will need to be monitored for some time. - Nature, DOI: 10.1038/nature08368, 28 Aug 09

A team studying the effect of diet on the cardiovascular system in mice have shown that a diet low in carbohydrates could lead to artery damage. Three groups of mice each received a different diet: a standard mouse type, a western diet (high in fat) and a low-carb, high-protein version. Scientists looked at the resulting cholesterol levels and incidence of atherosclerosis (the build up of fatty plaque deposits in arteries) in the mice. They found that after 12 weeks, the low-carb diet had no effect on cholesterol levels. However, one sixth more of the mice eating the low-carb diet had developed atherosclerosis compared with the standard diet. The western diet produced an increase in atherosclerosis of around one tenth. This effect could be due to a reduced ability of bone marrow calls to clean the fatty deposits from the arteries for mice on a low-carb diet. The team conclude that a balanced diet is by far the best option for overall health, coupled with regular exercise. They recommend that at least one-third of the diet should be made up of starchy foods such as bread, rice and potatoes. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.090799510624, 24 Aug 09

A team of scientists have developed a patch which could help the heart to heal after damage. Heart attacks often cause irreversible damage to the heart muscle, leaving survivors more prone to further attacks or heart failure. The team took immature heart cells from newborn rats, and placed them onto a biodegradable 'scaffold'. They then exposed the patch to chemicals which encouraged the cells to grow, before transplanting it into the abdomens of rats. After a week, the patch developed a network of blood vessels and muscle fibers and could be grafted onto the rat's heart. Full integration, where the patch was able to synchronize its beat with the surround tissue, was seen within a month. It is hoped that the procedure may lead to treatments in humans. But because most heart attack patients are old, multiple surgeries can pose a significant risk. The technique could show more promise for mending damage to other organs such as the liver and bladder, and development is already underway. - Proceeding of the National Academy of Sciences, DOI: 10.1073/pnas.0812242106, 24 Aug 09

Researchers using mice have shown how the Leishmania parasite, transmitted by sand flies, establishes infection. Leishmaniasis is a disfiguring and potentially fatal parasitic infection that affects some 350 million people worldwide. Contrary to previous research, they found that it is not the sand flies’ saliva that helps the parasite establish an infection, but a secreted gel called PSG. It is produced by the Leishmania parasite, and forms a plug which blocks the gut. This forces the sand fly to regurgitate to dislodge the plug and feed properly, which simultaneously deposits the parasite and some of the gel into the human body. After the bite, the immune system is quickly activated and many immune cells rush to the site, including macrophages. Macrophages usually engulf and digest foreign particles, but the Leishmania parasite is able to persuade the macrophages not to digest them, instead providing them with nutrients and a safe place to replicate. To study how the parasite produced this effect, the team injected the parasite under the skin of mice. The parasites were mixed either with saliva or with PSG. Parasites injected with PSG attracted five times more macrophages to the bite site than parasites mixed with saliva, and the PSG was responsible for making the macrophages provide nutrients. The gel protected the parasites so that more survived beyond 48 hours, and eight times as many cells were infected. Further work will concentrate on developing a synthetic version of the gel which may provide protection against infection. - PLoS Pathogens, DOI: 10.1371/journal.ppat.1000555, 21 Aug 09

A team of scientists studying mice have found a target that could lead to an effective way to kill colon cancer cells. Scientists developed treatments for many types of cancer in the past by targeting the epidermal growth factor receptor (EGFR). This belongs to a group of proteins that signal cells to reproduce; if the cells can no-longer reproduce, then the cancer cannot spread. However, the drugs designed to target the receptor have shown very little effect against colon cancer, so the search is on for new targets. The new study identified the ERBB3 receptor (a close relation to EGFR) as a candidate. They genetically blocked the newly-identified receptor in mice predisposed to colon cancer, and saw that the mice rarely went on to develop the cancer. They also tested human colon cancer cell lines, and observed increased cell death when the ERBB3 protein was removed. The researchers will now test medicines that inhibit ERBB3 in an attempt to produce the same effect as genetic manipulation. The hope is that medicines of this type will be very effective at killing colon cancer cells where previously others have failed. - Journal of Clinical Investigation, DOI: 10.1172/JCI36435, 17 Aug 09

Scientists have harnessed the power of magnetism to guide stem cells towards damaged tissue in rats. The team coated stem cells with iron nanoparticles. This allowed them to be moved by an external magnet around the body, to the site of injury. It also allowed their path to be tracked using MRI (magnetic resonance imaging) scanners. They used endothelial progenitor stem cells, which circulate in the blood and are involved in the healing of blood vessels. They become endothelial cells, the cells that line the blood vessels. To test the stem cells, they used rats with vascular injury, where the endothelial cells that line the carotid artery had been stripped away. They then injected the tagged stem cells into the bloodstream. The group of rats exposed to a magnetic field showed a five-fold increase in the number of tagged cells at the site of injury after 24 hours. Iron nanoparticles have already been approved for medical use in the USA, so human trials for this application could begin in three to five years. The technique could have widespread uses, especially in situations where medicines can be harmful to healthy tissues, for example in chemotherapy. - Journal of the American College of Cardiology, DOI: 10.1016/j.jcin.2009.05.014, 16 Aug 09

By blocking the production of a faulty protein in mice, researchers have delayed the onset of motor neuron disease, improved mobility, and extended life-span. Motor neuron diseases affect the cells that control movement. Most types are 'sporadic', but some are genetic. Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is genetic. It is caused by a mutation on the X-chromosome so the disease only fully affects males. Previous research showed that SBMA is caused by a mutation in the androgen receptor. The mutation produces a faulty protein, which accumulates in the body causing damage to the motor neurons and leading to muscle weakness and wasting. In the past the team proved that Akt (a cell signaling protein) is able to increase clearance of the faulty protein. In this study they found that insulin-like growth factor 1 (IGF-1) activates the protein in the test tube. To see if the same was true in animals, they bred SBMA mice that expressed high levels of the growth factor in their skeletal muscles. The mice showed increased clearance of the faulty protein and therefore reduced accumulation in the tissue. Importantly these mice also had better mobility, put on weight and lived longer. For a disease that is currently untreatable, this is a step forward in understanding how it affects the body at molecular level and how it may be treated. - Neuron, DOI: 10.1016/j.neuron.2009.07.019, 12 Aug 09

Scientists using mice have discovered how early exposure to a common type of bacterium can lead to psychiatric disorders. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) causes problems such as obsessive-compulsive behavior, ticks and Tourette syndrome. It was known that streptococcal infection could lead to psychiatric problems but it wasn’t clear how. In this study researchers showed how a specific strain of streptococcus bacteria – GABHS – can cause PANDAS symptoms in mice. This common bacterium and causes sore throats, but in some people the body not only destroys the bacteria, but also attacks healthy tissue in the brain. To investigate the link between GABHS and PANDAS the team immunized mice with an inactive form of the bacterium. They saw that the mice produced antibodies to the bacteria and went on to show repetitive behavior similar to that seen in children with PANDAS. They also found that administering antibodies from the immunized mice into another set of mice could cause a similar psychiatric condition. This work shows how ordinary infections in childhood can lead to psychiatric disorders later in life. It opens up the possibility of identifying children at risk, and finding ways to prevent GABHS exposure leading to the development of PANDAS. - Molecular Psychiatry, DOI: 10.1038/mp.2009.77, 11 Aug 09

A group of scientists has harnessed the power of bee venom and used it to kill tumor cells in mice. By arming small particles dubbed nanobees with the bee venom melittin, they successfully delivered the toxin directly to tumors. If administered in high enough concentrations, melittin can destroy any cell by punching holes in the cell membrane. This mechanism is useful in the treatment of cancer, as cells find it difficult to adapt to survive such an attack. The challenge was to administer the toxin in a targeted way, so it only affected the cancer cells. To do this, the team attached a targeting agent to the nanobee particles containing melittin. The agent targeted the proliferating blood vessels of tumors; rapidly growing tumors require a vast supply of blood. The nanobees were tested on two groups of mice. One group had been implanted with human breast-cancer cells and the other had melanomas. After four to five injections, the breast tumors had reduced in size by a quarter, and the melanomas by nearly nine tenths, compared with untreated tumors. Despite the toxicity of melittin, the mice suffered from few side effects and there was little evidence of damage to non-cancerous cells. The carrier particles were harmlessly eliminated from the body by evaporation from the lungs after they had delivered the melittin to the tumors. The flexibility of nanobees suggests they could be used in a range of medical situations. Further studies will investigate their use for other tumor types, and their potential for treating patients. - Journal of Clinical Investigation, DOI: 10.1172/JCI38842, 10 Aug 09

Working with 'substitute' breast cancer stem cells and mice, scientists have discovered a chemical which can kill the cells that cause tumors to spread and return, even after seemingly successful treatment. The research, which involves a completely new way of identifying cancer medicines, could pave the way for a treatment that could kill cancer stem cells without harming other cells in the body. Evidence is growing rapidly that cancer stem cells are responsible for the aggressive powers of many tumors. Because the cancer stem cells are so rare, are relatively resistant to treatment, and are difficult to grow in the laboratory, the team worked on substitutes created from normal cells which were altered to adopt some of the properties of cancer stem cells. They then bombarded these substitute cells with chemicals to see if any had an effect. Screening 16,000 compounds, researchers found 32 promising candidates. Of these one stood out. Salinomycin, an antibacterial and anti parasite compound normally used for chickens and pigs, killed 100 times more cancer stem cells than standard chemotherapy. It killed not only the substitute cancer stem cells, but also real ones, and reduced breast tumor growth in mice. The mouse studies showed that it seemed to suppress the genes that are linked to particularly aggressive tumors and that lower chances of survival. Further research will establish if the chemical has the same effect in humans. - Cell, DOI: 10.1016/j.cell.2009.06.034, 13 Aug 09

Researchers have reversed the symptoms of glaucoma in rats using medicated eye drops. Further tests on a small number of human patients also showed promising results. Glaucoma is caused by increased intraocular pressure (pressure inside the eye). This gradually causes damage to the optic nerve, which eventually leads to blindness. Researchers used rats suffering from glaucoma to test eye drops containing nerve growth factor (NGF). They saw that NGF caused a reduction in the damage and death of the optic nerve cells. Further tests on three human patients showed the drops improved vision in two patients whilst preventing deterioration in the third, after three months. It is not known exactly how NGF causes this improvement. It may be that chemicals are triggered in the presence of NGF that prevent the cells from dying, or it could be that NGF encourages new connections to be made within the nerve fibers to compensate for those lost due to damage. However, the possibility that this non-invasive treatment could help prevent deterioration or even improve vision is exciting news, opening up a whole new way of treating glaucoma and preventing unnecessary loss of sight. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0906678106, 3 Aug 09

Mice have grown new teeth from stem cells implanted into the jawbone. Stem cell technology has been used before to produce tissues, but in a limited way. This is the first time a study has shown that a few cells can go on to produce a fully functioning organ. The team began by removing the upper molars from five-week-old mice. They developed a seed-like bioengineered tooth tissue containing stem cells and the genetic instructions necessary to form a tooth, and transplanted the tissue into the jawbones of mice. The implanted cells developed into fully formed teeth with an identical structure to normal teeth. They were hard enough to allow chewing and showed typical responses to pain, due to the development of an extensive network of nerve fibres. Gene activation was tracked using a green fluorescent protein and was seen to be identical to that in normal tooth development. Further tests will look at side effects of this technique, and whether it could work in humans. However, it is an interesting starting point in organ replacement techniques, showing that stem cells can become whole organs. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0902944106, 3 Aug 09

Scientists have shown for the first time that it is possible to stimulate the heart to heal itself without the use of stem cell technology. Heart muscle cells are undifferentiated in a fetus, so are able to multiply and grow to create new heart muscle tissue. However, as the fetus develops, these cells become differentiated and, it was previously thought, no longer produce new tissue. This has consequences in adults when damage occurs to the muscle, for example in heart attacks and in congenital heart defects. Recent research has indicated that differentiated heart muscle cells have some limited ability to multiply and grow after injury. So researchers tested a number of growth factors in mice and rats in an attempt to raise this level of growth. Increasing a growth factor called neurregulin1 (NRG1) significantly boosted multiplication of the heart muscle cells. This led to regeneration of the heart muscle, and the heart worked better. Further studies will look at how NRG1 works on the heart. Tests will be carried out in pigs, which are more closely related to humans. The possibility that adult heart muscle cells can be stimulated to multiply and grow is exciting, as a viable alternative to stem cell therapy. - Cell, DOI: 10.1016/j.cell.2009.04.060, 23 Jul 09

A blue dye – similar to that used in M&Ms and licorice allsorts – can help protect rats' crushed spinal cords from further damage. Spinal cord injuries often become worse a few days after the initial damage. Previous studies with rats have shown that this secondary damage is due to the action of a molecule called ATP, which is responsible for transporting energy around the body. After injury ATP swamps the area, over-stimulating the nerve cells, stressing them and eventually killing them. Previous attempts at blocking the ATP receptors have been successful, but the steroid used is toxic to the heart. It is also too big to cross the 'blood-brain barrier', so must be injected directly into the spinal cord. Scientists discovered that the blue food dye, called Brilliant Blue G, had a similar structure to other ATP receptor blockers, but had the advantage of being smaller. They injected the dye into rats with spinal cord injury and saw that the rats could move their back legs after 10 days, and some were able to walk again after six weeks. The compound has already passed rigorous testing for food safety. In this study the researchers saw no signs of toxicity, although it did temporarily turn the rats' eyes and skin blue. It is still unclear whether the dye will work in humans, and it is likely that a much larger dose will be needed. However, this is an important step towards developing therapies for spinal cord crush injury. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0902531106, 28 Jul 09

Scientists have discovered that the natural hosts of a strain of SIV develop AIDS when infected. This overturns a longstanding belief that such viruses had no effect on non-human primates. The subspecies of chimpanzee concerned were studied in their natural habitat over nine years in Gombe National Park in Tanzania. The SIV strain, called SIVcpz, is a direct ancestor of HIV-1, responsible for human infection. The team found that the chimpanzees infected with SIVcpz developed AIDS in the same way humans do after infection with HIV. Both SIVcpz and HIV target immune cells called CD4+ T-lymphocyte cells and over time their numbers dramatically reduce. This weakens the immune system, until it is so weak the human or chimpanzee is classified as having AIDS. Because SIVcpz works by exactly the same mechanism as HIV in humans, it is hoped that further study of the virus will lead to a better understanding of the disease. Scientists should then be able to find new targets for better treatments and the development of effective vaccines. - Nature, DOI: 10.1038/nature0820, 23 Jul 09

A new kind of stem cell, that doesn't involve destroying embryos, has produced new life. iPS cells are made from ordinary skin cells, and were hailed as a breakthrough two years ago when they were produced by genetically reprogramming human skin cells. Questions remained about whether iPS (induced pluropotent stem) cells could act like embryonic stem (ES) cells and morph into any cell type in the body. Now two teams of researchers have answered these questions, by producing live mice. Stem cells were coaxed from the skin of adult mice and then reprogrammed using a virus. Because the cells can't create a placenta, the researchers then combined the new stem cells with cells that provide a placenta. While there were abnormalities and unusual deaths with some of the first generation of mice, one team produced enough normal mice this way to create hundreds of second and third generation mice. The work shows that the new type of stem cells satisfy the most stringent criteria of embryonic stem cells – the ability to make a mouse entirely from cells in a dish. These type of stem cells generate less controversy than ES cells, which scientists have been studying for more than a decade, because ES cells involve the destruction of embryos. The mice will be valuable in studying how cells are reprogrammed. - Nature, DOI: 10.1038/nature08267, 23 Jul 09

Researchers have used mice to pinpoint what goes wrong in aneuploidy, which includes the most common genetic disorders involving chromosomes, usually an extra chromosome. Aneuploidy includes Down syndrome and Edwards syndrome, and often causes pregnancy loss. The researchers were looking at mutations of a particular gene in mice, to determine its role in colon cancer development. However, during the study they noticed that the mice carrying one copy of a mutation in the Bub1 gene had fewer offspring. Further studies found that this effect was confined to female mice. If a mother's egg had a mutation in one of the copies of Bub1 then she was more likely to have fewer offspring that survived until birth. They also found that the mutation was more harmful the older the mice were, which is the same for aneuploidy in humans. Bub-1 works as a checkpoint in cell division, controlling the spindles which pull the chromosomes apart during cell division. It is likely that the mutation disrupts this process, resulting in extra chromosomes in the egg cells. Further tests will study the mutation in more detail to see if this is the case, and whether the mutation is present in humans. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0903075106, 17 Jul 09

Using mice, scientists have pinpointed the molecule which is responsible for making allergic reactions more severe. The team studied patients who had experienced anaphylaxis (a severe allergic reaction) during surgery. They found that these patients had very high levels of the hormone IL-33. Further studies using mice showed that this hormone significantly increases inflammation. Inflammation is triggered during anaphylactic shock. This reaction is often so severe that constricts the airway, leading to breathing difficulties and even death. By blocking the IL-33 hormone in mice the researchers were able to reduce the inflammation to non threatening levels. The next stage is to study the hormone in more detail to better understand why it causes such severe inflammation. In the future, IL-33 inhibitors could change the way we treat anaphylaxis and could save many lives. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0901206106, 16 Jun 09

Fat Busting Pill?

An artificial hormone has reduced body weight and fat mass in mice, and fast. Previous studies suggest that single treatments for obesity cannot reduce weight by more than about one tenth. While surgery remains the closest thing we have to a cure, this is very invasive. So many studies are looking at ways of using hormones to reduce weight. Researchers combined the sequences of two hormones (glucagon and glucagon-like peptide-1) to produce a synthetic molecule that activates multiple receptors. The two hormones are similar in structure, but have different functions. Their potential is the subject of current obesity research after scientists showed they can increase the use of calories by the body. After just a week on the new hormone, mice lost a quarter of their weight and their fat mass reduced by over a third. Follow-up after a month showed even greater loss – reductions of nearly a third and over two thirds respectively. The technique of activating multiple receptors in a single treatment could open up a whole new way of thinking about the treatment of obesity. - Journal: Nature Chemical Biology, DOI: 10.1038/nchembio.209, 13 Jul 09

A vaccine that reverses rabies in mice after just one injection may pave the way to cheap, effective prevention of the deadly disease. Current vaccines involve the immediate injection of inactivated viruses and are very effective, but patients need a month-long series of five injections. Researchers used a live virus that was attenuated (weakened). This stimulates a more powerful immune response, but live viruses can themselves cause disease. By changing a protein on the surface of the virus they could ensure it was safe, but also produce a stronger immune response.  To make sure the genetically modified virus did not cause disease, the team injected the vaccine directly into the brains of mice which were either normal or had weakened immune systems. Neither of the groups of mice showed signs of rabies. They also injected adult mice with a very virulent strain of the virus before giving the vaccine. When the vaccine was given within three days of exposure, the mice did not develop rabies. The vaccine also worked against future infections when injected three weeks before exposure. There are concerns that an aggressive immune response could cause damage to the nervous system, so further tests will study this aspect in more detail. But there is the prospect of a single injection that could protect people against rabies for life. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0905640106, 6 Jul 09

Rapamycin was found in soil on Easter Island 40 years ago. The antibiotic is normally used to prevent organ rejection and is being tested as a cancer treatment. Now, scientists have shown that it also extends the lifespan of mice. Most significant, their study reveals molecular pathways involved in ageing. The mice were aged about 18 months, the equivalent of about 60 years old in humans, when they received the drug. Rapamycin was able to extend their lives by an extra third, compared with the average lifespan of this strain of mouse. This surprised the team, but it is good news because it would be much better to treat people only when they approach old age. Further research into the medicine and how it works on ageing is essential. One of rapamycin’s side effects is that it suppresses the immune system (which is why it is used in organ transplants). So the next step is to look at the protein affected by the drug – mTOR – and attempt to design new compounds that target this pathway without the immune related side effects. - Nature, DOI: 10.1038/nature08221, 8 Jul 09

Using GM mice, scientists have shown that caffeine can reduce dementia symptoms. To confirm that the mice were good models for Alzheimer's, the scientists first tested the mice for behavioral and memory impairment. At around 18 months old – late middle age for mice – they got caffeine in their drinking water. They received the equivalent to a human drinking five cups of coffee a day, and two months later they performed better in the memory tests than mice that got no caffeine. The mice also performed as well as mice of the same age without Alzheimer's. Analysis of the brains of the caffeine-dosed mice showed reduced levels of a protein called beta-amyloid. It is beta-amyloid that is responsible for forming destructive plaques in the brain, causing symptoms such as dementia. The team concluded that caffeine reduces the level of beta-amyloid by affecting production of related enzymes and suppressing inflammatory changes in the brain. The reduction in Alzheimer's signs and symptoms, coupled with the fact that caffeine is relatively safe, means these findings are promising. However, clinical trials will be needed to see if caffeine has the same protective effect in humans. - Journal of Alzheimer's Disease, DOI: 10.3233/JAD-2009-1087, 7 Jul 09

The largest animal study ever on the cancer-causing risk (carcinogenicity) of chemicals could have profound implications for the species used in such testing, the numbers of animals used, and the accuracy of current tests. Scientists at Oregon State University found that acceptable levels of at least one carcinogen may be 500 to 1,500 times higher than currently believed. They also showed that using thousands of trout may give more accurate results than a hundred laboratory rats in assessing the risk of some chemicals. Currently, to assess real-world risks of exposure at low levels over a long time, high doses of chemicals are tested over a much shorter period in rats. There have always been concerns about the accuracy of data obtained in this way, but the methodology has been dictated largely by costs and logistics. The new study, using trout, shows that traditional methods may overestimate actual risks by a factor of 1,000 for a class of toxins called polycyclic aromatic hydrocarbons (PAH), although it also shows that current tests for others called aflatoxins may be more accurate. As one of the researchers, Professor George Bailey, told Science Daily: 'The whole foundation of modern toxicology is that the dose makes the poison. You can die from eating a few tablespoons of ordinary table salt at one time, but that doesn't mean that table salt is a poison at the doses that humans normally consume. With compounds that we know can cause cancer, the real question is how much is too much. What we have found is that traditional approaches to making that evaluation, which are almost always based on studies done at very high doses with laboratory rodents, may not always give us answers that are reasonably accurate.' This is one reason why the results of such toxicity tests have been interpreted cautiously, a factor which may have led to further exaggeration of risk and the setting of safety thresholds that are too high. In the new study, the scientists exposed over 40,000 trout to a low dose of a type of PAH, which can cause liver cancer. Professor Bailey said: 'We can do experiments with trout in large numbers at very low cost, about 5% of what a rodent study would cost. For most studies of carcinogens, exposing 2,000 rodents would be a huge project. For us, working with 2,000 trout is a pilot study.' The team found that a tolerable threshold for human exposure to this toxic chemical would be 500 to 1,500 times higher than that found using rodent studies and currently permitted by the US Environmental Protection Agency. So the study suggests that past methodology to assess the danger of some of the most common carcinogens in the world may, or may not, be accurate. Professor Bailey explains: 'In the past, our regulatory agencies have done the best they can with the data they have available. The key is that now we have animal models that can far more accurately determine the real cancer risk some compounds pose, and in biochemical detail that's more valuable than the kill-them-and-count-them approaches of the past. It may be time for government agencies and medical researchers to reconsider the way we approach carcinogen research.' This may have implications for the new EU regulations on chemicals and their safe use, REACH, which will require some animal testing and is being phased in across member states over a 10-year period. - Chemical Research in Toxicology.

Blocking the action of a gene called Sirtuin-1 reduced the symptoms of type 2 diabetes in rats, scientists have found. People with Type 2 diabetes suffer from high blood glucose concentrations due to insulin resistance and increased glucose production. To create a similar condition in rats, the researchers put the rats on a four-week diet of high-fat, fructose-rich meals. Sirtuin-1 is a gene responsible for regulating glucose production in the liver. The researchers blocked Sirtuin-1 in the diabetic rats by injecting them with a fragment of genetic information. This fragment – called an antisense oligonuclotide – interrupts and blocks gene expression and can be targeted to specific genes. After Sirtuin-1 inhibition, the rats were more sensitive and responsive to insulin. The rate of glucose production fell back to normal levels, resulting in a decrease in the blood plasma. Thus the Sirtuin-1 gene is a cause of type 2 diabetes symptoms. The results of this study are consistent with a recent mouse study which showed that decreased expression of Sirtuin-1 led to better insulin sensitivity. The next step is to develop inhibitors targeted to Sirtuin-1 in the liver. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0812931106, 22 Jun 09

Using fish, scientists have discovered a signaling pathway that could be used to treat skin cancers (melanomas). The pathway, PI3K (phosphoinositide 3-kinase) had a major effect on the progression of cancerous melanomas in zebrafish. Zebrafish are ideal for studying skin cancer as the melanomas are similar to those seen in humans, and the fish themselves are easy to observe because of their light-colored, almost transparent skin. Signaling pathways regulate cell division, migration and death. The pathways form a complex network to relay these various commands to cells. But when the signalling molecules mutate, the result is often excess cell division which can lead to cancer. The team looked at two major pathways called Ras and PI3K. They found fish often developed melanomas which progressed rapidly if molecules in these pathways were mutated. The discovery that PI3K was directly involved indicates that it could be a suitable target for melanoma therapy. The mutant zebrafish also passed on the mutations to their offspring. In this they were strikingly similar to the human inherited syndrome FAMM (familial atypical mole and melanoma). This study highlights a potential target for therapy, but also gives scientists new insights into the mechanisms of melanomas, revealing other possible targets. Further research into these models will be required to see if they're as promising as this initial study indicates. - Disease Models and Mechanisms, DOI: 10.1242/dmm.001149, 25 Jun 09

Scientists using mice have developed a new way to deliver gene therapies. By using hollow particles to deliver a gene into cells, they successfully reversed hemophilia symptoms. Gene therapy can be used to treat diseases caused by a mutated or missing gene. The technique involves delivering a correct copy of the gene. However, current methods haven't worked too well in patients; often the gene binds at the wrong place in the DNA or doesn't integrate itself into the cell. The new technique using very small nanoparticles to deliver the genes aimed to overcome these problems. The team also used a genetic element known as Sleeping Beauty to help integrate the genes into the cells' DNA. Hemophilia is a blood disorder caused by a lack of a protein called Factor VIII (FVIII). FVIII helps blood clot after injury; so lack of the protein means blood cannot clot effectively. The team loaded the nanoparticles with the gene that produces the FVIII protein (along with the Sleeping Beauty element), and covered the particle with chemicals to seek out and selectively bind to specialized liver cells. They then injected the particles into mice and monitored the effect on blood clotting time and levels of the FVIII protein. At five and 50 weeks the clotting times of the treated mice were about the same as in normal mice, and much longer than in the untreated group. At 50 weeks the levels of Factor VIII in the blood of mice given the nanoparticles were also the same as in normal mice. Using nanoparticles with the Sleeping Beauty genetic element seems to work well, and could represent a viable way to deliver gene therapies for various diseases. - Journal of Clinical Investigation, DOI: 10.1172/JCI34332, 8 Jun 09

Researchers have created a GM mouse that develops Parkinson's disease. This mouse will allow them to study progression of the disease and test new treatments without extensive use of monkeys. Parkinson's disease is caused by a mutation on chromosome 12. There are a number of different mutations known to cause the disease, however the team looked at just one - LRRK2. Because the genes responsible for causing Parkinson's are very long, traditional genetic techniques are unsuitable. So the researchers used a technique called BAC (bacterial artificial chromosome) which uses sections of bacterial DNA to introduce the gene into the mouse DNA. The mice produced using this technique showed all the signs of Parkinson's seen in humans. This includes slowed movement and brain cell degeneration. At 10-12 months the transgenic mice were largely immobile with severe defects in their muscle function. However, treatment with levodopa (used to treat Parkinson's in humans) reversed these defects. This suggests that LRRK2 is being expressed in the mice in the same way as in humans, so the mice offer the first model of Parkinson's disease based on a known genetic mutation, replicating features of the human disease. - Nature neuroscience, DOI: 10.1038/nn.2349, 7 Jun 09

Researchers have designed small particles - ‘nanoparticles' - that are able to selectively bind to plaques in arteries. This could enable treatments for furred arteries to be delivered directly and selectively. Atherosclerosis is caused by the build up of fatty substances such as cholesterol in arteries which eventually form plaques. The plaques can grow to cause blockages, slowing down blood flow, and when they rupture they spill their contents into the blood which can lead to dangerous clots. The team developed the nanoparticles to target plaques that are more susceptible to rupture. They chose to use lipids, because they clump together in water-based solutions (such as blood) to form spheres called micelles. They then placed a protein on the outer surface of the micelle to bind to the surface of plaques. The scientists labeled the micelles using a fluorescent protein before injecting them into mice fed on high-fat diets. The micelles were allowed to circulate in the mice for three hours before imaging the arteries to detect fluorescence and determine where the micelles had bound. The greatest intensity of fluorescence was around regions containing most of the plaques, which indicates that the micelles were binding specifically to the plaques. Further analysis showed they bound all over the plaques, but more frequently at the shoulder region, the thinnest part of the plaques and the most likely region to rupture. This work means it may be possible to deliver treatments directly to the site of rupture in the plaques most prone to bursting. - Proceedings of the National Academy of Scientists, DOI: 10.1073/pnas.0903369106, 1 Jun 09

Why does Huntington's disease lead to the death of brain cells, whilst causing negligible damage to cells elsewhere in the body? The culprit could be a protein recently characterized in mouse studies. Huntington's disease is caused by a mutated gene that produces a faulty version of a protein called Huntingtin. This mutated protein is found throughout the body; so why does it only cause damage to brain cells? In particular why is cell death mainly confined to the corpus striatum, the area of the brain responsible for movement? To answer these questions scientists looked for proteins within the corpus striatum that interacted with the mutated Huntingtin protein (mHtt). They found a protein called Rhes which bound much more strongly to the mutated form than the healthy one. The team then administered combinations of mHtt, healthy Htt and Rhes to brain cells taken from mice. Half the cells died within 48 hours when mHtt and Rhes were present together. They found that Rhes had an impact on clumping of the mutant Huntingtin. In all of the cells in the body containing the mHtt, the cells were protected by clumping of the mutant protein. But in the presence of Rhes, the protein clumps broke down. It is thought that this dispersion of mHtt is responsible for damage to brain cells. The team is now looking at whether removing Rhes from mice with Huntington's disease can stop the brain cells from dying, or at least slow down the deterioration. - Science, DOI: 10.1126/science.1172871, 5 Jun 09

Scientists have identified a gene implicated in up to one fifth of breast cancers. The good news is that studies in mice seem to show a commonly-used blood pressure drug appears to reverse the effects of the gene. The team began by searching for genes which are over-expressed in tumors, to identify possible targets for treatments. They backed up previous findings - the most commonly expressed gene in breast cancers is ERBB2. However they also identified a new gene AGTR1 which was over-expressed in 10-20% of patients. This gene codes for an angiotensin receptor involved in regulating blood pressure. A drug currently on the market targets this specific receptor; therefore the researchers tested its effect on AGTR1 type tumors. They took mice and implanted tumor cells into their breast tissue. When treated with the drug called Losartan, they found that tumors containing the AGTR1 gene shrank by nearly a third. Although the drug was only effective for this type of tumor, the fact that the drug is already on the market is very promising. Further studies will look at Losartan in more detail to determine how it works and whether it will be an effective treatment for these types of tumors in humans. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0900351106, 1 Jun 09

Scientists have found a way to turn adult cells from pigs into any tissue in the body. The team took cells from a pig's ear, and used a virus to deliver a mix of chemicals into the cells. These chemicals are designed to alter the cells, and reprogram them. After being infected with the virus, the adult cells reverted back to a state similar to that of stem cells and were able to then develop into many types of tissues. This technology could have many applications. Pigs organs are of a similar size to humans and function in similar ways, so have potential in animal-to-human organ transplants. But there are potential problems relating to virus transmission and rejection of the organs. Even after genetic manipulation, the human immune system recognizes pig cells or organs as foreign and attacks them. However, the new technique opens up the possibility of manipulating the immune cells precisely in the pig so they are effectively ‘humanized'. This would lower the chances of rejection, as the transplanted organ would be more compatible with the human immune system. This work could also lead to better models of human disease, by precision modification of genes in the stem cells to express human genes for diabetes or other diseases. There are implications for farming too, as the technology would allow the manipulation of the pig genome to ensure healthier pigs whose growth could be regulated. - Journal of Molecular Cell Biology, DOI: 10.1093/jmcb/mjp003, 3 Jun 09

Transgenic mice have been used in research for the last 20 years, and have made significant contributions to biomedical research. Last week scientists in Japan produced the first transgenic monkeys. The findings, reported in Nature, have important implications for studying genetically inherited diseases. Many news outlets have picked up on this story, including The Times, which featured an opinion piece by Hugo Rifkind. It has also appeared on many other sites, including on the Pro-Test blog. Transgenic mice have been revolutionary in biomedical research. They have made it possible for scientists to study the effects of specific genetic modifications in particular cells or organs (see our page on genetically altered mice). As helpful as these mice models can be, there are still many differences between mice and humans. It is beneficial to have the best models possible of human disease in these mice, which is why transgenic mice have proved so useful. However, research will often progress to larger mammals and eventually non-human primates before humans, to give the most accurate indications of the effect on humans. The prospect of being able to produce a transgenic monkey carrying the human gene for a particular disease could lead to more reliable animal research. There have therefore been studies in the past where teams have attempted to produce transgenic non-human primates. The first transgenic NHP was a macaque named ANDi in 2001. ANDi was engineered to produce the same protein as the current study, but was unable to pass the gene onto his offspring. The ability to pass genes on to further generations is key to producing a good research model, as it is too costly and difficult to insert new genes into every required animal. This is why the results of this paper are potentially very important, as the team report that they produced five marmosets, all of which express a green fluorescent protein (GFP), which was passed onto their offspring. As exciting as this research is, it is important to stress that the results do not mean this technology is ready for widespread use now, and there are many concerns to address before it does. The ability to produce transgenic mice has led to a significant increase in the number of mice used in research, and some worry the same will happen with non-human primates. However, it is difficult to say at this point whether this will be the case, and it is possible that this technology could actually reduce the numbers of animals that are used in research, as they will be better models for human disease. Also - yes the team in Japan have effectively produced glowing monkeys, which fluoresce under ultraviolet light. But no - this is not typical of the kind of animal this technology is likely to produce in future. The introduction of the green fluorescent protein was carried out to test the technology, to ensure that the gene was expressed in the offspring. It is actually a good choice of gene, as the fluorescence of cells can be tracked using a simple UV light, rather than more invasive procedures. If this technique does eventually go on to produce colonies of monkeys with inserted genes, they will be models for incurable genetic diseases such as Alzheimer's and muscular dystrophy. We believe that this type of research has considerable potential for medical advancement. However, individual projects must be scientifically justified and subject to ethical evaluation. In addition, researchers must act responsibly and humanely to the animals. We believe the public should also be well informed in this area of research, with scientists prepared to openly discuss the implications - Nature.

When scientist Loretta Mayer set out to alleviate diseases associated with menopause, she didn’t realize her work could lead to addressing world hunger and feeding hundreds of millions of people. The Northern Arizona University researcher and her colleagues at NAU and the University of Arizona identified a nontoxic chemical technology that when applied to rodents, caused infertility in rats, which feast on crops intended for human consumption. "This environmentally neutral approach, that has never been available before, will reduce the damage rice-field rats cause in countries that depend on rice as a main food supply," Mayer said. Rodents consume or damage up to 50 percent of pre-harvest rice crops. Due to the large-scale cultivation of rice worldwide, if rice production were to increase by 10 percent, "this would feed about 380 million people a year," Mayer said. "We can easily increase rice production by 10 percent by reducing rodent fertility in half." She said this noninvasive approach is more humane than poison, which takes several days to kill rodents and seeps into groundwater, harming other animals and possible food sources. The sterilization technology derived from Mayer’s research, done by Patricia Hoyer and and Glenn Sipes at UofA, investigated potential damage caused to ovarian follicles in women exposed to certain chemicals in industrial settings. Of particular interest was a chemical compound known as 4-vinylcyclohexene diepoxide, or VCD, typically used in manufacturing rubber tires, polyesters and plastics. She found that low, nontoxic doses of VCD in mice sped the menopausal process and rendered them infertile. She dubbed this new animal model of accelerated menopause "mouseopause." Mayer and her colleagues have developed a product called ContraPest that incorporates the chemical sterilization treatment into bait. The bait is put into strategically placed stations that lure rodents into cages too small to attract or affect other animals. "No rat or mice I know can resist a little hole," she said. ContraPest is being tested in Indonesia—the largest producer of rice in the world, and is currently being registered for rodent-population control in Australia. "We are testing it in Indonesia, and then our next target site will be in the Philippines. From the Philippines we go to Vietnam," Mayer said. Scientists adapt the product to different rodent species at SenesTech, the Flagstaff-based company that grew out of Mayer’s work on the NAU campus. Named after the word senescence, meaning approaching an advanced age, the young company hopes to create a number of beneficial products. Mayer and her team of researchers also are adapting the technology platform for population management of other animals. They are formulating a product, ChemSpay, for use in population management of wild animals such as deer, coyotes, foxes, raccoons, horses, buffalo and elk as well as cats and dogs. "What we are doing right now is we are preparing the translation of this technology to dogs and cats. We have already completed six months of study in dogs. This could have a tremendous impact on reducing the number of animals in shelters," said Mayer noting that not only is the method a cost-effective way to avoid surgical spaying, there’s a global impact to canine management most people don’t realize. "Dogs are huge vectors of disease throughout the world," she said. "In India, every two seconds someone is bitten by a dog. The tragedy is that every 30 minutes someone dies from rabies. If you continue to vaccinate against rabies, you won’t be able to make a dent. You have to combine rabies vaccinations with fertility control." She hopes to address rabies problems on the rise in West Africa, India and China. Australia hopes to put the technology to use in managing its kangaroo, wallaby and camel populations. New Zealand, Spain and the United Kingdom also are in line to put ChemSpay to use. She said luring students to the research team was easy. "We want them involved with hands-on research and field experience," she said. "The first question I ask interested students is if they have empty passport pages they are ready to fill." Biology graduate student Anna Mae Burd recently returned from training international colleagues in the Philippines. She is initiating field tests in Indonesia with graduate student Nyo Me Htwe. Me Htwe has been working by the side of Mayer’s partner, NAU researcher and SenesTech’s chief scientific officer Cheryl Dyer adapting the bait to different rodent species. - Inside NAU, Vol. 6 No. 18, May 20, 2009

Cold Virus Fights Cancer Selectively

Scientists have managed to modify the cold virus so that it only targets and damages cancerous cells. Cancer cells suppress the body’s immune system, allowing viruses to enter. Once there the viruses replicate rapidly, and could therefore be very effective therapy. However, the problem has been administering the virus without damaging other tissues. Traditional viral vaccinations such as those for influenza and mumps, involve administering a weaker form of the virus, so the immune system learns to recognize it. However, in the case of cancer, the virus is administered to cause damage to the cells; therefore the weakened form is not strong enough. The team therefore modified the cold virus. They attached DNA fragments to the outside of the molecule. These fragments allowed the virus to be recognised by the liver. The principle was that it would then be possible to administer a full strength virus to fight the cancer, as it would then be inactivated once it reached the liver and would not be toxic. When tested in mice, the team saw a 50-fold reduction in the replication of the virus once it reached the liver, and the mice given the virus lived twice as long as untreated mice with cancer. This approach could lead to the development of an easy to use therapeutic which is specific, not only for cancer, but for other diseases too. - Public Library of Science Pathogens, DOI: 10.1371/journal.ppat.1000440, 22 May 09

Studies using rats have linked chemicals released by tumors with depression. Cancer patients often become depressed once diagnosed. This is often put down to the psychological effect of finding out the bad news. However, this new study suggests that this depression could be caused by chemicals released by the tumor, which then travel to the brain. The team conducted tests on about 100 rats, some of whom had cancer. They used a swimming test, commonly used to measure depression, and found that the rats with tumors were less motivated to escape than those who did not have cancer. Rats are good models in this case, as they are not aware that they have the disease, therefore the depressive behavior cannot be attributed to psychological issues. Looking at blood samples and brain studies of the rats, the team saw the animals with tumors had higher levels of chemicals called cytokines. Cytokines are chemicals produced by the immune system which are known to increase with disease. A study earlier this month looking at mice with inflammatory disease linked an increase in cytokines with depression, due to the action of their metabolites. This discovery could form a target for medications, designed specifically to prevent depression in cancer sufferers. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0811949106, 18 May 09

Two studies have indicated that it is the physical force of a heart beat which triggers blood stem cells to produce new blood cells. Hematopoietic stem cells (HSCs) are the cells in bone marrow and embryos which are able to produce any type of blood cell. In blood disorders such as leukemia, if scientists are able to isolate a few of these cells and encourage them to produce blood cells in the lab, it could be revolutionary, as patients would no longer require bone marrow transplants from a matched donor. A team working on zebrafish screened over 2,500 chemicals to study their effects on HSC production. They saw that chemicals which enhanced the blood flow caused an increase in HSCs. Further tests indicated that nitric oxide (NO) was responsible for regulating the HSC development, and could be the mechanism by which the body converts the physical forces into chemical signals. However, it was clear that without the physical force of circulation, the HSCs were unable to develop. The other team extracted HSCs from mice embryos. They then used a device to propel fluid over these cells to look at how the stress of friction produced by the flow of the fluid affected blood cell formation. They found that the force of the blood flow promoted blood cell formation and increased colonies of HSCs. The aim of studies such as these are to develop a way to coax stem cells into producing blood forming cells in the lab, which could then be used in the treatment of blood disorders. - Cell, DOI: 10.1016/j.cell.2009.04.023, 15 May 09

Scientists believe they have pinpointed why thalidomide causes birth defects when given to pregnant women. There have been many theories as to why thalidomide caused limb defects when it was used to combat morning sickness; however few have had enough data to back the ideas up. The problem with studying thalidomide is that the drug is broken down into over 100 different compounds as it passes through the liver. This new study identified and isolated many of these compounds for the first time, allowing them to be tested in chickens. Chickens had to be used, as thalidomide does not cause birth defects in commonly used laboratory rodents such as mice and rats. The team found a compound that was similar to a thalidomide break down product in both its structure and chemical composition. This compound, CPS49 was administered to the chickens at a similar point as when thalidomide was given to pregnant women. The results showed that CPS49 caused severe limb defects, leaving the rest of the embryo untouched. They conclude that this is because the embryos core blood vessels were suitably developed at the time, but the limbs had not yet acquired an adequate blood supply. This paper therefore puts the ability of thalidomide to block the development of new blood vessels as the most likely cause of its side effects. The aim is to produce a compound similar to thalidomide without the side effects, as it is currently an important therapeutic in the treatment of leprosy and multiple myeloma, a form of cancer. - Proceedings of the National Academy of Scientists DOI: 10.1073/pnas.0901505106, 11 May 09

A team of scientists studying mice has pinpointed a gene involved in memory impairment, such as that seen in Alzheimer’s disease. The HDAC (histone deacetylase) family has long been implicated in learning and memory, and inhibitors of the family have been shown to improve learning. However the specific mechanisms behind this improvement were unknown. The team were interested in the effects of the HDAC1 and HDAC2 members of the family in mice. Initial studies involved two groups of mice bred to over-produce either HDAC1 or 2. Results showed that increased HDAC2 expression caused impaired memory formation, but increased HDAC1 showed no effect. They then bred a group of mice that did not express HDAC2, and saw that memory formation was enhanced in comparison to normal mice. They concluded that HDAC2 impairs memory formation. When the mice bred to over-produce HDAC2 were injected with a HDAC inhibitor, they showed an increase in memory function. Memory enhancement seen previously using these inhibitors must be due mainly to the inhibition of HDAC2, rather than the other members of the family. Further work will include designing more specific inhibitors for HDAC2. These could improve learning and memory function in patients suffering from neurodegenerative diseases such as Alzheimer's. - Nature, DOI: 10.1038/nature07925, 7 May 09

Scientists using mice believe they have identified the mechanism which determines whether fatty deposits in the arteries are harmless or potentially fatal. Fatty deposits in the arteries, called plaques, build up from the teenage years onwards. They are normal, and mostly harmless. However, a small percentage have the potential to burst, leaking their contents into the blood stream. This can restrict blood flow, and lead to clots which prevent blood flow altogether. The team discovered that the inner core of the plaques contained dead cells. They believed that a substance released by these cells was responsible for weakening the surface of the plaque, leaving it more vulnerable to rupture. The aim of the researchers was to identify what causes these dead cells to build up in the plaques. A gene called CHOP was thought to be a good candidate, as it plays a crucial role in cell death. The team therefore engineered ‘knockout’ mice (that did not express the CHOP gene), and compared the effect of a high-fat diet on them and on normal mice expressing the gene. The mice without the CHOP gene tended to produce smaller plaques which were less susceptible to rupture. So the CHOP gene is probably involved in this process and provides a potential target for therapy. Future treatments could focus on preventing the harmless plaques in young people from becoming dangerous, or soothing those that are susceptible to rupture as the body ages. - Cell Metabolism, DOI: 10.1016/j.cmet.2009.03.003, 6 May 09

Scientists have developed a possible way to immunize animals against HIV using the common cold virus. So far it has been tested in guinea pigs, and seems to be effective against a wide range of HIV strains. Scientists have faced two major problems in attempting to immunize against HIV. Using the actual virus to produce a vaccine (as with other viruses such as measles) is too dangerous, and HIV mutates rapidly. Mutation is problematic as it can change the shape of the virus dramatically, so the immune system is no longer able to recognize it. So the team studied the virus to locate a region that was crucial to its function, and unlikely to be altered as the virus mutates. But such a small region by itself would not activate the immune system. So to activate a response, they needed to use another virus to introduce the HIV segment. They used the rhinovirus which causes the common cold. This technique is quite complex, as the shape of the HIV segment must stay the same to allow the immune system to recognize it. The process involved systematically testing millions of ways of combining the HIV segment with the rhinovirus to discover the best method. Although the guinea pigs seemed to be protected against a large number of HIV types, the response was very small and slow. But the results prove that the technique has potential and warrants further investigation. - Journal of Virology, DOI: 10.1128/JVI.00184-09, 1 May 09

Scientists have discovered a mouse which carries the genetic mutation responsible for increased susceptibility to eczema, and eczema-related asthma. The mutation occurs in the gene for filaggrin, a protein found in the skin. The skin plays a crucial role as a barrier, preventing water loss and making sure pathogens, chemicals and allergens don’t reach the immune system easily. The filaggrin protein is key to maintaining this barrier; if the gene is mutated, the shape of the protein is changed so the barrier becomes weak. This can increase water loss, causing ichthyosis vulgaris (a common inheritable disorder of dry skin). Scientists also recently linked the mutation to eczema and eczema-related asthma, as it also lets antigens and allergens pass through the skin and reach the immune system. An unexpected mutation in laboratory bred mice causing a condition known as 'flaky tail'. The team discovered that these mice carry the filaggrin mutation so could offer insights into the precise role of filaggrin, and its role in eczema and related asthma. As with many genetic conditions of this nature, inheritance of the mutation does not mean the individual is certain to develop the condition; but it increases the chance they might. So the team hope to use the mouse to explain how environmental factors influence development of the disease. One such theory is that exposure to pets in infacy increases the likelihood of developing asthma. - Nature Genetics, DOI: 10.1038/ng.358, 1 May 09

Researchers studying mice have shown that an increase in excitability in calcium channels in the brain could explain recurrent seizures. Calcium channels are found throughout the body. The channels located in the brain allow calcium ions to pass into the brain cells, where they are responsible for the brain’s electrical activity, something which becomes imbalanced in epilepsy. It is believed that some people have a genetic susceptibility to epilepsy, but the team wanted to study how people without this disposition develop the disorder. Previous studies have suggested that calcium channels (specifically the ones found in the hippocampus region of the brain) increase in number after initial seizures. It is thought that this increase causes an imbalance in the brain, leaving the brain more susceptible to further seizures. The team wanted to find out whether the thalamus also contributes to the development of epilepsy. After they induced seizures in mice, the number of calcium channels increased in the thalamus, but not in the hippocampus. This suggests that the gene that codes for calcium channels can be switched on, increasing the channels in the thalamus and the likelihood of seizures. These new findings will help in the search for better therapies for epilepsy. Further studies can concentrate on reducing the channels in the thalamus, or preventing the gene from being switched on. - The Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.0198-09.2009, 8 Apr 09

Researchers have developed a single injection that is capable of producing long-term local anesthesia in rats. By packaging the anesthetic in fat-based particles called liposomes, it was released gradually, rather than all at once. Local anesthetics are often used during and after surgery to manage pain. They work by blocking the nerve signals to the area where pain is being experienced, stopping the pain signals from reaching the brain. Previous attempts at developing long-lasting local anesthetic formulations have stumbled; they haven't lasted long enough, or have been toxic to the body and the surrounding tissues. The concept of packaging the anesthetic has been investigated, but past packaging materials have caused tissue damage too. Liposomes show promise as they are able to encase the anesthetics without causing damage or toxicity. The team tested liposomes containing the anesthetic saxitoxin in rats. After a single injection, the anesthetics blocked the nerve signals for two days. They also tested saxitoxin in combination with a steroid called dexamethasone, which is known to enhance the action of anesthetics. The rats which received this combination showed nerve blocks that lasted a week. Tissue analysis after administration did not show toxicity in either muscle or nerve cells. This could be significant not only for pain following surgery, but could also be used to treat chronic pain, without the problem of addiction associated with narcotics. The slow-release ability of liposomes could also have implications for a variety of other medicines. The team is currently working to optimize the formula to make it last longer without becoming toxic, with a view to starting clinical trials. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0900598106, 13 Apr 09

Scientists using mice have carried out tissue transplants without the need for life-long anti-rejection medication. After a transplant, immunosuppressants need to be administered to prevent the immune system from attacking and rejecting the new tissue. However, these medicines reduce the patients’ ability to resist infection, and increase the risk of cancer and high blood pressure. So scientists developed a new antibody complex which alters the immune system without the need for immunosuppressants. This complex only needs to be administered in the short term, before the transplant. It works by stimulating immune cells known as T regulatory cells, which subdue the body's immune system. The complex was administered to mice for three consecutive days to suppress their immune systems, before transplant of pancreatic cells. After the transplant, the numbers of T regulatory cells dropped, returning to normal in about two weeks. By this time four fifths of the mice had accepted the transplanted tissue. After 300 days there were no signs of rejection. Transplants are considered accepted if they haven’t been rejected after 100 days. While cautious, the team are encouraged by the results. They will try transplanting other organs in mice before looking to see if the technique will work in larger mammals. -The Journal of Experimental Medicine, DOI: 10.1084/jem.20082824, 30 Mar 09

Researchers have developed a new pain-free method of vaccination which does not involve an injection. Using mice they have shown that it is possible to deliver a vaccine orally by combining it with protective friendly bacteria. Most traditional vaccines given orally would be digested in the stomach and become inactive. However the team found that by combining the vaccine with probiotic bacteria (found in dairy products such as yogurt) they could stop the vaccine being destroyed by digestion. The vaccine can therefore reach the small intestine, where a powerful immune response can be stimulated.  They fed an oral anthrax vaccine to one group of mice; another received the traditional injected vaccine. Exposure to anthrax bacteria showed that oral administration of the vaccine was just as effective and produced a much more powerful immune response than the injected vaccine. This method is pain free which is an obvious advantage. Other benefits include a lack of side effects. Traditional vaccines require an additive to stimulate the immune system which is thought to be responsible for side effects such as dizziness, vomiting and swelling. These additives are not required in the oral vaccine because probiotics are natural stimulators of the immune response. The team believes it could be possible to develop oral vaccines for breast cancer and a range of infectious diseases such as flu. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0900029106, 17 Apr 09

Researchers have found that an electrical current, delivered through an implant in the spinal chord, can aid movement in rodents showing Parkinson’s symptoms. The study is based on the principles of deep brain stimulation (DBS), a highly effective treatment using electrodes implanted deep into the brain. However, the surgical procedure required to implant the electrodes in the brain is highly invasive, so alternatives are being investigated. Researchers used rodents (rats and mice) with symptoms of Parkinson’s, implanting a tiny electrode into the spinal chord. They applied an electrical current which travelled up the spine and into the brain. Three seconds after beginning the stimulation, the rodents no longer showed symptoms and could move normally. This approach is safer and much more straightforward than implanting electrodes into the brain. A constant sense of vibration is a side effect, but reduced risk and lower doses of medication are convincing benefits. More research is needed but these findings are very promising. The procedure is currently being tested on monkeys and, if successful, human trials could begin in the next few years. Science, DOI: 10.1126/science.1164901, 20 Mar 09

Researchers studying a gene called DISC1, previously implicated in schizophrenia, have seen evidence that it is essential for normal brain development. Their study showed that when this gene is mutated, the growth of brain cells is disrupted, leading to the development of schizophrenic symptoms. Studies of mouse embryos showed large amounts of DISC1 in brain stem cells and normal brain growth. Further investigations on adult mice brain stems also showed high levels of the gene. However, when the scientists simulated presence of the mutated gene, the cells failed to grow and divide. The mice were observed in their cages and did a swim test (commonly used to test the effectiveness of antidepressants). The DISC1-deficient mice did not swim for long and were ‘skittish’ in their cages, behavior associated with mental illness, and schizophrenia. Interestingly, the team discovered that protein produced by the gene inhibits the same enzyme, GSK3beta, as lithium. Lithium is commonly prescribed to patients with mental illness as a mood stabilizer. In DISC1-deficient mice treated with a molecule that inhibits the enzyme, brain stem cells return to normal, producing new neurons, and restoring normal behavior. The identification of the part of the DISC1 protein that affects the enzyme may provide new ways of treating schizophrenia. The next stage is to identify additional variations in the DISC1 gene. - Cell, DOI: 10.1016/j.cell.2008.12.044, 20 Mar 09

UV Lights Reduce TB Spread

Scientists using guinea pigs have shown that installing UV lights could reduce the transmission of TB (tuberculosis) in hospital wards. TB, a bacterial infection, is spread from person to person through droplets in the air when they cough. TB spread in hospitals is worsening as drug resistant strains become more common. Researchers investigated the potential of UV light (to damage the bacteria’s DNA) and negative ionizers (a way of ‘cleaning’ the air) to reduce TB infection rates in hospitals. They pumped air from TB infected wards into three separate enclosures containing guinea pigs. The first group received air exposed to UV light in the ward, the second, air treated with negative ionisers, and the final group received untreated air. The results were significant. A third of the group exposed to untreated air got infected with TB, compared with one seventh receiving ionized air, and less than one tenth of the animals exposed to UV-treated air. Effective ventilation systems increased the impact of UV treatment by directing the treated air downwards and the potentially infected air upwards. The scientists therefore recommended that the lights be used in combination with fans. Plans are already underway to set up UV lights in a hospital in the UK. The chest clinic at St Mary’s Hospital, London, will be the first hospital to install this relatively low-cost solution. - PLoS Medicine, DOI: 10.1371/journal.pmed.1000043, 17 Mar 09

Researchers have developed a new approach in the search for treatments for Duchenne muscular dystrophy (DMD). Based on the principle of concealing the genetic errors that cause the disease, the treatment has been successful in dogs with the canine version of DMD. DMD is one of nine versions of muscular dystrophy and is caused by a faulty protein, produced by a mutated dystrophin gene. It is a paralyzing and often fatal muscle-wasting disease. Associated with the X chromosome, it affects only boys, starting very young (between 2 and 6 years) and almost always resulting in early death. As yet there is no treatment, but strains of mice and dogs suffer ‘naturally’ from the disease, allowing scientists to study it in more depth. The new treatment is based on existing technology known as exon-skipping, which uses sections of DNA-like molecules as ‘patches’ to conceal the mutations in dogs. Because mutation occurs in different places in the dystrophin gene, scientists tried multiple patches called morpholinos. They succeeded in restoring protein and muscle function. Previous studies have successfully injected morpholinos into the bloodstream of mice; this study suggests morpholino injection can be successful in much larger animals. The results open up the possibility of using morpholinos against the multiple mutations that occur in human DMD, using injection as the method of delivery. However, further research is needed as large doses of the patches were required. This would be expensive and could be toxic. Also, the treatment did not effectively prevent or slow heart muscle deterioration, so a more specific delivery system may be needed. - Annals of Neurology, DOI: 10.1002/ana.21627, 13 Mar 09

Scientists have created a strain of the human AIDS virus which is able to infect and proliferate in monkeys. This discovery is a major breakthrough in the search for a vaccine against AIDS. The team found that it was possible to infect macaque monkeys with HIV by altering a single gene in the human version of the virus, producing a strain called simian-tropic HIV-1 (stHIV-1). Previously the best monkey models of AIDS had involved infection with SIV. SIV is often called a ‘cousin’ to HIV, as it causes a disease similar to AIDS in some monkeys. But SIV is not identical to HIV; for instance, the microbiocide gell Carraguard seemed effective in monkeys but did not show such promising results in humans. When injected into the monkey, stHIV-1 reproduces almost as much as HIV does in humans. However, the animal then starts to suppress the virus and therefore does not develop AIDS. While this in itself may provide interesting clues to suppression of HIV, the model may need further changes to perfect it for testing therapies and vaccines. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0812587106, 2 Mar 09

Antibodies able to bind to a protein in the brain show promise in mice for preventing fatal prion diseases like vCJD (variant Creutzfeldt-Jakob Disease). vCJD is a progressive neurodegenerative prion disease affecting both animals and humans. Prion diseases involve a change in shape of a protein, PrP, through interaction with infectious prion proteins. This faulty protein then builds up in the brain causing cell death. It is thought that antibodies could disrupt the binding of prions with PrP, so preventing the conversion. The team began by producing a 3D-picture of the structure of the binding between antibodies and PrP using X-ray crystallography. This meant they could visualize exactly which parts of the two proteins bound together, and were then able to test a range of antibodies to see which were the most effective at blocking conversion of PrP. Using a range of antibodies in mice they confirmed that, when PrP proteins in infected mice could not change shape, early brain damage was reversed and the onset of prion disease was prevented. The monoclonal antibody ICSM18 was found to work best in both cell and mouse-based studies. Human versions of the antibody are currently in production for future human trials. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0809170106, 3 Mar 09

Scientists have developed an experimental monoclonal antibody treatment. Using the treatment, they were able to neutralize a variety of flu germs in mice, including H5N1 avian flu. Monoclonal antibodies are produced by the immune system in response to foreign entities, such as viruses. They work by neutralizing the virus, providing lasting immunity specific to the strain. However, the problem with the flu virus is that it constantly mutates into new strains, so new flu vaccines are required each year. The team identified a stem that supports the rapidly mutating head of the virus,. By searching a library of known human antibodies they were able to find existing antibodies that targeted this stem, which does not mutate so rapidly. They administered the antibodies to one group of mice before exposure, and another group after exposure to the flu virus. Surprisingly, the antibodies proved effective when administered both before and after exposure and against a range of different flu viruses, raising the hope of being able to develop a single treatment to treat many different strains. Because large quantities of this type of antibody can be made relatively quickly, it could be used in combination with antiviral drugs to prevent or treat flu during an outbreak. - Nature Structural and Molecular Biology, DOI: 10.1038/nsmb.1566, 22 Feb 09

Using rats, scientists have clarified the role of the liver in the clearance of a toxic protein thought to be the cause of Alzheimer’s disease. The findings are promising as they could lead to a new target in the development of new treatments for the disease. The new study is based on the principle that the liver could be involved in clearing a damaging protein called A-beta from the blood, which in turn could help A-beta clearance from the brain. To investigate this, the team looked at the process in reverse by manipulating the livers of laboratory rats to reduce clearance, and so increase the levels of A-beta in the blood. They observed that the raise in A-beta levels in the blood reduced the rate at which the protein was cleared from the brain. So levels in the peripheral bloodstream affect levels of A-beta in the brain. These findings contradict past research suggesting that the circulatory system acted like an A-beta ‘sink’, as this data clearly shows that the liver is the primary drain. The team believes that helping the liver to clear A-beta protein from the blood could provide a new way of combating the detrimental neurological effects of Alzheimer's. - Journal of Alzheimer's Disease, DOI: 10.3233/JAD-2009-0964, 24 Feb 09

A team of researchers have pin-pointed the gene which controls the production of tooth enamel in mice, called Ctip2. When the gene had been ‘knocked out’ in mice, so it no longer functioned, their teeth lacked adequate enamel coating to protect them. They believe the Ctip2 gene controls cells called ameloblasts, involved in the formation and growth of cells that secrete enamel. The gene has been previously identified as having a role in immune function and development of the nervous system. However, its role in the production of tooth enamel is a new discovery, and could lead to new possibilities in dentistry, including repairing damaged enamel and preventing cavities. The inner portions of teeth have already been grown using stem cells, but due to lack of enamel they were very fragile. This new discovery raises the possibility that in the future it will be possible to ‘grow’ whole teeth in a laboratory as an alternative to false teeth. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0900568106, 26 Feb 09

Scientists have developed a way to prompt cancerous cells to kill themselves in mice. Traditional cancer treatments such as chemotherapy and radiotherapy work by damaging cancer cells. Once the cells sustain enough damage a trigger is activated, which leads to programmed cell death, called apoptosis. One problem is that often the cells aren’t damaged enough to undergo apoptosis and instead get repaired. The remaining cells are responsible for the low success rate of some current treatments, so cancers can often return, even after multiple cycles of treatment. The new strategy uses small DNA fragments called Dbaits which mimic the two broken ends of DNA that come from cellular damage and trigger apoptosis. Lab mice injected with Dbaits before radiotherapy had most of their cancer cells wiped out compared with only third to one half eliminated using radiotherapy alone. What’s more, there was no damage to healthy tissue, which often occurs during radiotherapy. This technique could lower the dose of radiation required and would be especially useful for treating cancers that are known to develop resistance to radiotherapy, such as brain and skin cancers, and. The researchers are hopeful that clinical trials could start by the end of 2010. - Clinical Cancer Research, DOI: 10.1158/1078-0432.CCR-08-2108, 15 Feb 09

Working with mice, researchers have identified a protein that may help thousands of people in the USA who contract Lyme disease each year. Lyme disease is caused by bacteria that live in the midgut of ticks. It is transmitted when the ticks bite humans and animals. Infection causes fever, tiredness, headache, muscle and joint aches. The researchers found a metal transporter responsible for the transport of manganese. It is thought that transporters such as these are essential for the bacteria to establish infection in mammals by recruiting key nutrients. When they genetically engineered bacteria to lack the metal transporter, the bacteria could not grow in mice. This discovery may lead to new strategies for thwarting Lyme disease; the next step is to understand the importance of manganese in the bacteria. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0812999106, 13 Feb 09

Researchers have further evidence that more than one gene is involved in people with genetic-based autism, with the number of genes involved being linked to the severity of the disorder. Autism is not classed as a single disorder as there is a great diversity in symptoms and severity, which vary from patient to patient. The group of autistic spectrum disorders (ASDs) ranges from severe autism to the milder Asperger Syndrome. Studies of patients with ASDs have shown that bigger brains mean more severe behavioral problems. The team found two genes that when mutated can cause autism-like symptoms in mice. They discovered that mice with mutations in either one of these genes had larger brains, whereas mutations in both genes resulted in an even larger brain. In female mice, those with a single mutation became socially impaired, and more so if both the genes were mutated. The scientists concluded that an interaction between the two genes influences both brain growth and sociability. Future work will study how genes, environment and medicines affect these animals' autism-related traits. This could lead to the development of therapies that target the signaling pathways between these interacting genes to alleviate some of the symptoms of ASDs. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0804428106, 10 Feb 09

Scientists using animals have discovered that a naturally occurring proteinadministered to specific areas of the brain could slow or stop the progression of Alzheimer’s Disease. Alzheimer’s disease is a neurodegenerative disease, caused by the progressive degeneration and eventual death of brain cells - neurons. This study involved a protein called brain-derived neurotrophic factor (BDNF) responsible for supporting the survival of existing neurons and encouraging the growth and development of new neurons. They used a range of animals including mice, rats and monkeys with induced, or naturally occurring, neuron degeneration. The test groups were injected with BDNF in the parts of the brain responsible for formation and consolidation of memories. All the animals in the test group got better at a variety of learning and memory tests. Their brain cells survived longer and made more connections. This method is particularly promising as it acts directly on dying cells in the memory ‘circuits’ of the brain, preventing their death and improving their function. This means BDNF treatment could provide long-lasting protection against neurodegenerative diseases such as Alzheimer’s Disease. - Nature Medicine, DOI: 10.1038/nm.1912, 8 Feb 09

Recent research shows that an increased level of a protein found in the brain can provide protection from Parkinson's Disease in mice. In Parkinson’s, brain cells – neurons – slowly become impaired and messages get disrupted. Because the area of the brain involved is responsible for movement, the body’s muscles are unable to function in a smooth and coordinated manner. Researchers engineered mice to have extra copies of a gene for a protein called Nrf2, produced by astrocyte cells in humans and in mice. Astrocytes are brain cells which have been found to play a protective role against neuron death. When they exposed the mice to a chemical known to cause Parkinson’s, the mice did not develop the disease. The chemical was not toxic and the neurons were saved. Because Parkinson’s is usually only diagnosed once neuron damage has occurred, the next step is to carry out long-term experiments in mice to see if it is possible to reverse the damage once it has taken place. This will depend heavily on whether the neurons are dead or just dysfunctional. More promising though is the potential for medicines that can activate Nrf2 to a high level. These would be potent therapies not only for Parkinson’s but also for other neurodegenerative conditions such as Alzheimer’s and Huntington’s, where astrocytes have also been implicated. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0813361106, 5 Feb 09

Researchers using mice believe they have found a way to help stem cells regain their normal function in leukemia patients. In those suffering from leukemia, the stem cells responsible for producing blood cells often become faulty. Blood cells are produced in bone marrow by stem cells. In normal bone marrow there are known to be special places where the stem cells congregate, divide, and make new blood cells. Researchers discovered that a molecule called stem cell factor was responsible for attracting these cells to this niche. Previous studies had identified that cancerous leukemia cells also create niches in the bone marrow. The niches made by the leukemia cells over-produce the stem cell factor so a very powerful chemical signal is emitted, enticing normal stem cells into the cancerous niche. Once there, they become stuck, leading to a reduction of the stem cells in circulation and to a disruption of their normal function. The team therefore developed a way of blocking the release of these chemical signals in mice, using neutralizing antibodies. They saw that the stem cells no longer became stuck and began to produce healthy blood cells again. If this approach works in humans, it could help preserve healthy blood cells in people with leukemia. It could also make bone marrow stem cell transplants an option for more patients, allowing doctors to collect and bank patients' own stem cells for use after high-dose chemotherapy. - Science, DOI: 10.1126/science.1164390, 19 Dec 08

In a huge step forward in studying tumors, a mouse that mimics glioblastoma, the most common and deadly form of human brain cancer, has been developed. The mouse model closely follows the natural progression and development of human brain tumors. Researchers now hope to better understand the cancer, develop new treatments and test them more effectively. Until now, studying tumors in mice has largely relied on transplanting cancerous tissue from humans into mice with a weakened immune system, causing the development of a tumor in the mice. The downsides with this method are that the immune system is compromised (unlike in the human patient), and the fact that tumors normally develop from a single cell, not a piece of tissue. With this new method, a virus is used infect cells in mice whose immune systems are fully functional. The modified virus infiltrates adult mice cells with cancer causing cells, mirroring the randomly occurring mutations responsible for cancerous tumors. The scientists injected two well-known cancer causing genes into brain cells called astrocytes, which are thought to be the origin of glioblastoma in humans. Within a few months tumors displaying all the characteristics of glioblastoma developed in the mice. Cultured cells taken from these tumors showed structures called tumor spheres and displayed all the characteristics of cancer stem cells. Although the work published so far relates solely to glioblastomas, the team is currently using this methodology to investigate lung, pancreatic, and pituitary cancers. - Nature Medicine, DOI: 10.1038/nm.1863, 4 Jan 09

Small plastic disks impregnated with chemicals specific to fighting tumor cells and implanted under the skin can reprogram the immune system to attack tumors in mice. The chemical, called an antigen, is the substance that causes the body to generate antibodies which destroy foreign cells, such as those found in tumors. The problem with cancer is that the cells originate inside the body, and therefore often escape detection by our immune system. The theory is that if the immune cells can to be reprogrammed to recognize tumors as foreign, our own immune system could be used as a powerful weapon against cancers. Most previous work has focused on removing immune cells from the body, reprogramming them, and then re-injecting them back into the body. The new technique redirects the immune system from inside the body. This appears to be easier and more effective than other approaches. The implant sends out a strong signal attracting immune-system messengers. These messengers enter the implant, where they are exposed to the antigens specific to the tumor being targeted. This means that when they leave the implant, they are able to recognize the tumor as foreign. They then deliver this message to the immune system, which mounts an immune response against the tumor. Using mice that, if left untreated, would normally die from an aggressive cancer, they found that with this implant, 90% of the mice survived. This is the most effective demonstration of a cancer vaccine seen in animals so far. These implants should provide permanent resistance against cancerous cells, providing protection against relapses. There is also the possibility of loading the disks with other antigens to safeguard against an array of infectious diseases such as viruses. They could even redirect the immune system to combat conditions such as type 1 diabetes, which occurs when immune cells attack the body’s own pancreatic cells. - Nature Materials, DOI: 10.1038/nmat2357, 11 Jan 09

A trial using stem cells to treat spinal injury is to begin after promising results in animals. Patients with spinal cord injuries will be the first humans to receive cells derived from embryonic stem cells as the first ever clinical trial received the go-ahead from the US Food and Drug Administration after promising results in rat studies. The trial will involve patients who are paralyzed from the chest down, and hopes to ‘mend’ their spines by injecting injury sites with stem cells to restore connections and repair damage. This is a direct consequence of previous research with these cells involving rats. The promising results obtained showed that after treatment with the cells, mobility was improved in rats with spinal injuries. The treated rats could walk better, and post-mortems showed that the injected cells had multiplied in the injury site and restored lost connections. The hope now is that the same will happen in people. - NewScientist, 23 Jan 09