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Research Focus 2011:

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

 

Vaccine Against Streptococcus Pneumonia

Salmonella poisoning typically causes diarrhea. Now a modified salmonella is being trialed as a vaccine against Streptococcus pneumonia. Streptococcus pneumonia causes pneumonia, meningitis and bacteremia and is a leading cause of childhood deaths globally. The new vaccine use Salmonella bacteria as couriers to deliver key antigens that trigger an immune response against the target pathogen. As Salmonella bacteria are typically responsible for food poisoning they must be inactivated, or 'attenuated', before being used as safe vaccine vectors. Salmonella is a particularly versatile vector, possessing the ability to deliver antigens from a wide range of pathogens, and therefore could be used against viruses, bacteria and parasites. This most recent research has found a new, safer way to use Salmonella as a vaccine vector against pneumonia. The new method is based on detoxifying Salmonella lipid A, which is associated with most of the symptoms experienced as a result of adverse reactions to Salmonella vaccines. The new Salmonella strain was developed to synthesize a surface antigen – pneumococcal PspA – which induces the immune response. When mice were inoculated with this new strain they showed improved immunity to Streptococcus pneumonia and experienced less adverse symptoms thanks to the detoxification of lipid A. - The Journal of Immunology, DOI: 10.4049/jimmunol.1100339, 1 Jul 11

Cheap Treatment for Sleeping Sickness

Researchers are preparing for clinical trials of the first inexpensive oral treatment for Trypanosomiasis, the parasitic disease commonly known as sleeping sickness that is transmitted to humans by the tsetse fly. Sleeping sickness affects at least 30,000 people each year in central Africa but surveillance is difficult due to its rural distribution. Without treatment the disease is lethal, especially as it tends to affect populations with limited access to health services. The disease develops in two stages and presently two separate existing treatments are needed to target these, each requiring a complex course of injections. In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph. This is known as a hemolymphatic phase, which entails bouts of fever, headaches, joint pains and itching. In the second stage the parasites cross the blood-brain barrier to infect the central nervous system. This is known as the neurological phase. In general this is when more serious signs and symptoms of the disease appear: changes of behavior, confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is an important feature of the second stage of the disease. Without treatment, sleeping sickness is considered fatal. The new medicine (SCYX-7158) has successfully and safely treated infections in mice, beagles and macaques. It is based on a group of new compounds that contain the element boron. SCYX-7158 kills the Trypanosoma parasite, and is effective at both stages of the disease. Phase 1 safety trials are planned for later this year and as the medicine can be taken orally it is hoped that this new treatment can be developed as a simple, inexpensive medicine in pill form that can be administered at the rural village level. - PLoS Neglected Tropical Diseases, DOI: 10.1371/journal.pntd.0001151, 29 Jun 11

Reversing Rett Syndrome in Mice

New research using mouse models has shown that glial cells, which protect and support neurons in the brain, play a central role in preventing the severe symptoms of Rett Syndrome. Rett Syndrome is a debilitating autism spectrum disorder that occurs almost exclusively in girls and symptoms are visible by 18 months. Loss of speech, motor control and repetitive hand movements are characteristic of the disease. Seizures and severe digestive complications are also typical symptoms of the syndrome. Most patients of the disease live to adulthood and require full-time care. Rett Syndrome is caused by mutations in the gene coding for the protein MeCP2. It was previously thought that the disease was exclusively caused by a loss of MeCP2 function in neurons but this most recent research has demonstrated that these mutations also occur in glial cells. When these mutations to MeCP2 are induced in mice they demonstrate symptoms with characteristics similar to those expressed in humans with Rett Syndrome. Therefore mice are effective models for studying the disease. By inducing re-expression of MeCP2 solely in the mouse astrocytes, a particular type of glial cell, researchers were able to reverse Rett symptoms. Further research will look into whether other types of glial cell play a role in Rett Syndrome and investigate how astrocytes interact with neurons. It is hoped that the knowledge gained from further investigation will open up new treatment possibilities for Rett suffers. - Nature, DOI: 10.1038/nature10214, 29 Jun 11

Gene Repair Treats Hemophilia

About one in 30,000 boys are born with a defective gene that causes hemophilia B. Their blood does not clot, leaving them vulnerable to excessive bleeding. Currently treatment requires patients to have regular transfusions of blood clotting factors. Scientists have corrected a similar defective gene in mice, raising the possibility of new therapies that can target and repair this and other genetic defects. They injected the mice with a liver-targeting virus modified to carry the normal version of the blood clotting gene (F9) and enzymes called zinc-finger nucleases. The zinc finger nucleases are molecular scissors that cut the DNA helix at the F9 site. Breaking DNA induces the liver cells to make a repair. This then allows a working copy of the gene carried by the modified virus to be incorporated into the liver cell. Around 1 in 20 cells were repaired. When these cells went on to divide the repaired gene was duplicated, showing the repair was stable. This process produced enough repaired cells to reduce severity of hemophilia in the mice to mild. - Nature, DOI: doi:10.1038/nature10177, 26 Jun 11

Protein Linked to Cancer

Research in mice has shown how over expression (over production) of a small protein allows cancer cells to divide. Normally, when a cell's DNA is damaged, the cell has mechanisms to recognize this damage and prevent the damaged cell from replicating further. One such mechanism is called the intra-S-phase checkpoint. In breast and other cancers there is often an over production of a protein called cyclin-dependent kinase subunit (Cks). Until now the link between Cks over expression and malignancy was unclear. Now it seems that the Cks protein 'over-rides' the intra-S-phase checkpoint mechanism allowing damaged cells to continue dividing and so become malignant. This discovery was a lucky observation arising during basic biological research into cell division. The scientists used a chemical known as thymidine to temporarily halt the cell division process, and to artificially synchronize the growth of two different groups of cells – one with normal Cks expression, and the other with Cks over expression. To the researchers' surprise, the Cks-over expressing cells failed to stop dividing. The finding is expected to lead to the targeting of this mechanism with drugs and diagnostic techniques. - Proceedings National Academy of Science, DOI: 10.1073/pnas.1102434108, 22 Jun 11

Vaccine Shrinks Prostate Tumors in Mice

A vaccine containing a broad spectrum of tumor antigens delivered in a virus vector successfully treated 8 out of 10 mice with prostate cancer. Pieces of DNA from normal cells were added to a virus vector to make an anti-cancer vaccine. Injecting this vaccine into mice stimulated an immune response that ‘cured established tumors.' Previous attempts at creating vaccines against cancers have often failed because they either fail to elicit a sufficient immune response or have caused unwanted immune reactions against healthy tissue. This approach to cancer treatment holds promise because the vaccine is injected and there is no need for a drug delivery system that specifically targets the tumor. There is also the possibility that new vaccines can be created that contain DNA components tailored to other cancers. Human trials using this approach are expected within a few years. - Nature Medicine, DOI: 10.1038/nm.2390, 19 Jun 11

Enzyme Reduces Cancer Spread

Researchers have identified a protein trigger for tumor inflammation. Chronic inflammation is known to help tumors to grow and spread. By inhibiting this particular protein, scientists were able to decrease tumor growth and stop cancer progression in mice. The presence of cancer cells in the body often stimulates an immune response. This response can be beneficial but it often results in the accumulation of myeloid immune cells around the cancerous tumor. Scientists have long appreciated that cancer cells use these myeloid cells to help tumors grow and spread but exactly how this happens is not fully understood. Scientists have identified a number of molecules produced by cancer tumors which are responsible for attracting the myeloid cells. They discovered that by blocking an enzyme called PI-3 kinase gamma on the myeloid cells they prevent these cells from entering tumors. Blocking this enzyme reduced tumor growth and so has potential therapeutic value. - Cancer cell, DOI: doi:10.1016/j.ccr.2011.04.016, 14 Jun 11

CJD Research Potential for Alzheimer’s

Researchers working on treatments for the brain disorder Creutzfeldt-Jakob Disease (CJD) may have found a potential treatment for Alzheimer’s disease. Scientists discovered that two antibodies, which have been investigated for their potential in treating CJD, may also impact Alzheimer's disease. The antibodies, ICSM 18 and 35, have been found to block the accumulation of the protein 'amyloid beta', which attaches to the nerve cells in the brain in Alzheimer's sufferers. The accumulation of amyloid beta is associated with and may cause the reduced brain function and memory loss characteristic of Alzheimer's disease. This most recent study in mice suggests that the antibodies could not only be used in developing a treatment for CJD but also for Alzheimer's, which is a far more common form of dementia. Clinical trials of these antibody treatments will begin next year for their use against CJD. If successful, the trials are likely to be repeated for patients with Alzheimer’s. - Nature Communications, DOI: 10.1038/ncomms1341, 9 Jun 11

Heart Repair Initiated in Mice

Human hearts cannot repair themselves after a heart attack damages heart muscle. However zebrafish hearts can, and the human heart itself is capable of significant growth early in life, so scientists are seeking ways of stimulating human cells to repair the damage to heart muscle caused by heart attacks. Scientists have recently found that adult mouse hearts contain stem cells in the pericardium (layer surrounding the heart). Next, scientists stimulated these cells with a small protein called thymosin beta4 before causing limited damage to the heart muscle. This process gave rise to new heart muscle cells growing to repair the damaged area. The 'repaired' hearts were much stronger than untreated hearts. Now scientists are seeking more efficient ways to stimulate the stem cells resident in the heart. - Nature, DOI: 10.1038/nature10188, 8 Jun 11

Chemical in Apple Peel Strengthens Muscle

An apple a day really does keep the doctor away according to a new study in mice. A constituent of apple peel called ursolic acid has been found to reduce muscle wasting, also known as muscle atrophy, and promote muscle growth. Muscle atrophy affects most people at some point during their lives, either through aging or during illness. Mice that received ursolic acid in their diet had larger and stronger muscles. However, interestingly, the increased muscle mass did not increase their overall body weight because these mice had less body fat than those that were not fed the compound. Ursolic acid was also found to reduce their blood sugar levels, cholesterol and triglycerides. On analyzing patterns of gene expression the researchers found that cultured cells treated with ursolic acid possessed opposite expression patterns to those found in cells experiencing atrophy. Ursolic acid could therefore reverse atrophy. The study suggests that this could be due to its ability to influence the binding of hormones IGF1 and insulin to muscle cells, which alters muscle gene expression in such a way that atrophy is reduced and muscle growth is promoted. - Cell Metabolism, DOI: 10.1016/j.cmet.2011.03.020, 8 Jun 11

New Mouse Model for Hepatitis C

The hepatitis C virus infects in the region of 170 million people around the world and creates an increased risk of cirrhosis, liver failure and cancer. Because the hepatitis C virus only infects humans and chimpanzees it has been difficult to develop vaccines and other treatments. Now scientists have introduced two human genes into mice which make the mice cells produce 'entry factors' that allow the hepatitis virus to infect the cells and replicate. However, the rate of viral replication in the mouse is less than in humans so scientists also introduced a 'reporter gene' that produces detectable luminescence when the hepatitis virus enters a mouse cell. This new mouse model for hepatitis C will allow scientists to try out potential vaccines and other treatments to prevent the disease. - Nature, DOI: 10.1038/nature10168, 8 Jun 11

Protein Suppression Stops Leukemia Growth in Mice

Leukemia causing stem cells have been eliminated in mice by suppressing two proteins. Cancer stem cells are thought to be responsible for relapses in leukemia. The findings could lead to new treatments to prevent this. Researchers bred GM mice that didn't producing two naturally occurring proteins, called Bmi1 and Hoxa9. The lack of these proteins stopped leukemia developing in the mice. The findings apply to a type of leukemia that involved the mutation of a gene called MLL. This accounts for seven in ten cases of childhood leukemia. Only half of children diagnosed with MLL leukemia survive more than two years when given standard treatments. The protein Bmi1 was already known to be important for the survival of cancer stem cells. But targeting this protein on its own is not enough to eradicate MLL leukemia causing stem cells. By suppressing the protein Hoxa9 as well, the MLL mutation is unable to cause leukemia. Targeting these proteins together could lead to treatments for MLL leukemia. Researchers hope the findings will also help them understand the process by which leukemia cells originate - Cell Stem Cell, DOI: 10.1016/j.stem.2011.05.004, 3 Jun 11

Targeting Genes to Stop Breast Tumors

Some breast cancers do not respond to currently available chemotherapy. These tumors can contain cancer cells with stem cell-like properties which lack the molecular receptors that current medicines target. In 'triple-negative' breast cancers, cells lack molecular receptors for the hormones estrogen and progesterone and so they cannot be treated with breast cancer treatments that work by blocking these receptors. Such tumors make up an estimated 15% to 20% of breast cancers. They tend to occur in younger women, black women, and women carrying BRCA1 gene mutations. Recent work has characterized these cancer cells and found they have certain genes controlling their growth and proliferation. By blocking the activity of several genes, the researchers were able to suppress cell growth. Inhibiting drugs already exist for five of the genes identified as they are similar to genes involved in certain blood cancers. Studies have already shown that drugs designed to target these genes can stop breast tumors growing in mice and now medicines that target two of the genes identified are in advanced clinical trials. - Journal of Clinical Investigation, DOI: doi:10.1172/JCI44745, 1 Jun 11

‘Trojan Horse’ Brain Cancer Treatment Increases Lifespan

A novel ‘Trojan horse' method of treating brain cancer has increased the survival time of mice by one half. A cancer-killing virus was introduced into neural stem cells (NSCs) and these infected cells were introduced into mouse brain tumors. This increased the average lifespan of the mice from 63 to 93 days. The mice had been injected with a human form of brain cancer called glioblastoma, the most common and aggressive form of brain cancer. The average survival time for people with this condition is only 15 months. These brain tumors are also spread throughout the brain, making them difficult to target with conventional cancer treatments. Scientists can use viruses to target cancer cells, where they aggressively multiply and so kill the tumor. However, the body's own immune system often quickly destroys the virus before it can reach the tumor. To avoid this, researchers placed the virus inside NSCs which instinctively migrate towards cancer cells. The NSCs act as a ‘Trojan horse' to hide the virus from the immune system. Placing the virus inside the NSCs also improved the ability of the NSCs to migrate towards tumors. Researchers have warned that more research must be done to ensure that NSCs do not themselves contribute to cancer formation. - Molecular Therapy, DOI: doi:10.1038/mt.2011.100, 31 May 11

Skin Cancer Protein Identified in Mice

Scientists have identified a protein that suppresses skin cancer in mice. Researchers bred mice to lack a copy of the gene that makes the protein alpha-catenin. These mice developed a type of skin cancer called squamous cell carcinoma, the second most common form of skin cancer. Over 700,000 new cases of squamous cell carcinoma are diagnosed each year. Researchers also discovered the mechanism by which alpha-catenin stops cancer growth. Alpha-catenin was found to control the activity of another protein called Yap1. If activated, Yap1 can cause cancer. Researchers are now looking at possible ways to treat skin cancer by targeting the Yap1 protein. - Science Signaling, DOI: 10.1126/scisignal.2002177, 25 May 11

Prostate Tumors Reduced in Mice

Prostate tumors have been in reduced in mice using a medicine originally designed to treat obesity. Scientists used the medicine, called STO 609, to stop the production of an enzyme involved in metabolism, called CAMKK2. Without the enzyme, cancer cells are starved of the high levels of glucose they need to grow and multiply. The medicine reduced the growth of prostate tumors in the mice and stopped the cancer cells spreading to other parts of body. By reducing the growth of prostate tumors, scientists believe they could turn the fatal form of the disease into a manageable condition. The medicine was chosen to target a network of genes that produces the CAMKK2 enzyme. These genes are over expressed in cancerous cells compared to healthy cells. Scientists hope to start clinical trials of STO 609 within five years. - The EMBO Journal, DOI: 10.1038/emboj.2011.158, 20 May 11

Mouse Model of Human Immune System Validated

A mouse model of the human immune system has been validated by replicating the results of a recent human HIV clinical trial. A preventative HIV treatment, called tenofovir, was found to work similarly in both the ‘humanized' mice and large scale human clinical trials. The mouse model can now be used to search for novel HIV preventative treatments. The mice, called humanized BLT mice, have a fully functioning human immune system and so can be infected with HIV in the same way as humans. They are produced by introducing human bone marrow, live and thymus tissue into mice bred without an immune system of their own. Scientists were able to reproduce the results of a 2.5-year human study of the preventative treatment tenofovir. The topical medicine was found to reduce vaginal transmission of HIV by two fifths in humans. Applying the same experimental method to the mice, researchers found that tenofovir protected against vaginal HIV transmission in ninth tenths of the mice. After confirming the efficacy of the humanized BLT mice model, researchers then tested six further potential HIV prevention treatments. These medicines have not yet been tested in humans. All but one of the medicines showed partial or complete protection against HIV. These medicines are now being considered for testing in humans. - Journal of Virology, DOI: 10.1128/JVI.00537-11, 18 May 11

Possible Treatment for Muscular Dystrophy

About 100 boys are born with muscular dystrophies every year in the UK. All dystrophies cause progressive muscle weakness and in Duchenne muscular dystrophy this leads to an early death. One approach to treatment is to find molecules that boost muscle strength. After a mass screening program that tested chemicals on muscle tissue in culture, a chemical called SMTC1100 was tested on a mice that have muscular dystrophy. The mice given SMTC1100 were able to run 50% further in exercise trials and when SMTC1100 was given in combination with prednisolone, the steroid commonly taken by boys with Duchenne muscular dystrophy, fatigue was almost completely prevented and the mice were able to run 3.5 times further than with no treatment at all. SMT C1100 has already been tested in a phase 1 clinical trial on a small number of healthy volunteers and there were no safety concerns. However, the results of the trial were disappointing because insufficient amounts of the drug were being absorbed into the bloodstream and reaching the muscles. The drug is now being re-formulated before new clinical trials. - PLoS One, 4 May 11

New Hope for MS

Unlocking a key messenger protein in the body’s defenses could be a first step to new treatments for multiple sclerosis (MS) and other autoimmune diseases, suggest studies in mice with a form of the disease. The messenger protein is called granulocyte-macrophage colony-stimulating factor, or GM-CSF for short. The body’s immune of defense system comprises cells, processes and molecules that detect and respond to foreign agents, pathogens and injury to prevent harm and restore health, but in autoimmune diseases these attack healthy tissue instead. The study focused on a group of immune system cells called T helper 17 cells (Th17), which normally protect cells against invasion by pathogens, but are also known to be involved in autoimmune diseases in humans and animals. The researchers wanted to find out how these cells work. The researchers showed that GM-CSF could be a key culprit in the onset of MS, because without it, Th17 cells did not induce MS-like disease in mice with autoimmune encephalomyelitis (EAE), commonly used to study the biology of MS. This study revealed a pathway linking GM-CSF signaling and Th17 cells which turns out to be the main route to inflammation in the nervous system in autoimmune diseases like MS. In earlier research, the same team discovered a related mechanism in MS where another signaling molecule, interleukin-27 (IL-27), helped block the onset of symptoms in animals with an MS-like disease. Bringing the results of the two papers together, they suggest increasing levels of GM-CSF may cause MS, but increasing IL-27 may help quell an overactive immune system. If similar results are found in human blood samples, it may be possible to start looking for a new treatment for multiple sclerosis. - Nature Immunology, DOI: 10.1038/ni.2031, 24 Apr 11

Growing New Blood Vessels in Mice

Heart attacks and strokes could be prevented using a new method of blood vessel regeneration, according to research on mice. Blocked blood vessels can starve the brain and heart of vital oxygen and nutrients. Scientists treated the condition in mice by growing new blood vessels. Researchers grew new supporting cells in the blood vessel walls using a natural growth factor, called FGF9. When aged mice with blood vessel constriction were given FGF9, new blood vessels grew and blood flow improved in the mice. The new blood vessels also developed smooth muscle cells that enabled them to constrict and relax. Previous attempts at treating the condition focused on growing blood vessel lining cells. But the blood vessels produced were short lived and did not function well. Blood vessels grown from supporting cells, however, lasted for over a year. The finding provides a potential new treatment for vascular disease in humans. - Nature Biotechnology, DOI: 10.1038/nbt.1845, 17 Apr 11

Memory Loss Linked to Stress

Scientists have discovered how stress contributes to memory loss in old rats. High levels of the stress hormone cortisol have previously been linked to forgetfulness in old age. Researchers looked at two receptors in the brain that react to cortisol. Low levels of cortisol were found to activate one receptor and help memory function in aged rats. But when cortisol levels became too high, the second receptor was also activated. This reduced memory function in the rats, making it harder for them to navigate a maze. Using a new chemical, researchers were able to block cortisol production in cells. This improved the ability of the rats to navigate the maze. Understanding the mechanisms in the brain which affect memory could lead to treatments for conditions such as Alzheimer's. - Journal of Neuroscience, DOI: 10.1523/?JNEUROSCI.4046-10.2011, 12 Apr 11

Retina Grown in the Lab

Mouse retinas have been grown in the lab using embryonic stem cells. The technique could lead to treatments for human eye diseases. The retinas are the most complex tissue scientists have yet engineered using stem cells. Scientists hope to adapt the technique for human cells. Growing human retinas in the lab would open up the possibility of retina transplants for sufferers of eye disease. Age-related macular degeneration (AMD) and retinitis pigmentosa are the most common causes of blindness in old age. In these conditions retinal cells are gradually destroyed causing patients to lose their sight, often irreversibly. The possibility of treating these conditions with retina transplants is years away. More immediately, however, retina tissue can be used to study eye diseases and test potential medicines. Researchers grew the mouse embryonic stem cells in a chemical soup. This directed the stem cells to turn into specific retina cells. The eye cells grew into a complex two-layered structure, called an optic cup. The outer layer cells provide nutrients and support the retina, while the inner retina cells sense light. Researchers are now testing whether the optic cup can sense light and transmit information to the brain in mice.- Nature, DOI: 10.1038/nature09941, 6 Apr 11

Gene Linked to Lung Cancer Spread

Scientists have identified a genetic change that makes lung tumors more likely to spread to other parts of the body. The genetic change discovered in mice has also been found in human tumor samples. Researchers analyzed tumors from mice that were genetically modified to developed lung tumors. While all the mice developed lung tumors, only some of these tumors spread around the body. The process of cancer spreading to other parts of the body is known as metastasis. Metastatic cancer has a high chance of killing patients. Comparing metastatic to non-metastatic tumors, researchers discovered a difference in the activity of a gene called NKX2-1. Metastatic tumors had reduced activity of this gene. Researchers also analyzed human lung cancers. They found reduced activity in the NKX2-1 gene was linked to higher death rates. Understanding how tumors become more aggressive and metastasize could lead to new treatments for cancer. Targeting the NKX2-1 gene with medicines is difficult because it would mean turning it back on rather than turning it off. However, researchers hope to target other genes controlled by NKX2-1. - Nature, DOI: 10.1038/nature09881, 6 Apr 11

Stem Cells for Skin Repair

New treatments for chronic wounds could be developed following the discovery of stem cells that repair damaged skin tissue. Researchers identified stem cells in bone marrow that have the ability to turn into regenerative skin cells. Researchers transplanted fluorescent protein-bone marrow cells into mice, so they could track them as they moved around the body. Mice were then wounded and some were given skin grafts. In mice without skin grafts, very few stem cells travelled to the wound to repair it. Those given grafts had many stem cells moving to the wound site, healing the area quicker. Mice with skin grafts also produced high levels of a protein called HMGB1. HMGB1 was found to be released by damaged skin cells, mobilizing bone marrow stem cells into action and directing them to the wound site. This suggests that skin grafts don't simply cover wounds, but actively kick start the body into repairing the wound. It is thought the oxygen depleted environment caused by a skin graft could lead to the release of the HMGB1 protein. By understanding this mechanism of skin repair, scientists hope to find new treatments for chronic wounds, such as leg ulcers, pressure sores and burns as well as genetic skin diseases. Chronic wounds in UK patients cause pain and may require hospitalization. Their treatment costs the NHS more than a billion pounds every year. Researchers are now working towards medicines based on the HMGB1 protein to aid tissue repair. It is hoped to test treatments in animal models next year. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1016753108, 4 Apr 11

Multiple Sclerosis Reversed in Mice

The process of nerve cell degeneration in multiple sclerosis (MS) can be reversed, according to new research in mice. The finding could lead to new treatments for MS, if the disease is caught early enough. MS occurs when the body’s immune system attacks the long, thin extensions of its own nerve cells, called axons. This destroys parts of the brain and spinal cord, disrupting nerve signals and causing serious disability. Patients can suffer from fatigue, muscle weakness and spasms, difficulties with movement, eyesight, speech, and swallowing. It was thought that damage to axons resulted from the gradual destruction of the axon myelin sheath, a protective coating that speeds up the transmission of nerve signals. However, researchers found that mice in the early stages of a form of MS still have axons with an intact myelin sheath. This suggests that MS does not just result from myelin sheath destruction. Some of these axons were also able to spontaneously recover, perhaps explaining why MS patients can have periods of recovery followed by further relapses. The findings led researchers to propose a new mechanism of axon degeneration, called focal axonal degeneration (FAD). As this process is in principle reversible, it could lead to new treatments for MS, if the mouse studies are predictive of human MS and if the disease is caught early enough. However, the precise molecular mechanism behind FAD is still uncertain and more research is needed. Researchers were able to reverse this process of axon degeneration in the mice. It is thought that reactive oxygen and nitrogen molecules produced by the immune system result in the destruction of axons. By neutralizing these molecules, called free radicals, damaged axons appeared to recover. It is hoped such medicines could one day be used to treat MS in humans. - Nature Medicine, DOI: 10.1038/nm.2324, 27 Mar 11

Genes for Acute Myeloid Leukemia

Scientists have identified three types of gene mutation that lead to acute myeloid leukemia. The finding could lead to new treatments for the disease. Two newly discovered mutations were found to cooperate with the most common gene mutation in acute myeloid leukemia, called Npm1, to cause the disease. 2000 adults in the UK are diagnosed with acute myeloid leukemia every year. The disease results from the out-of-control production of abnormal white blood cells. These blood cells don't function properly, increasing the risk of infections and taking up space needed by red blood cells. The disease progresses rapidly and is often fatal within weeks if left untreated. Researchers created mice with the Npm1 gene mutation. This enabled normal blood cells to renew more efficiently. Self-renewal of cells can lead to cancer if not properly controlled. However, only a third of these GM-mice went on to develop acute myeloid leukemia, suggesting that other mutations are involved in the disease. Researchers then mutated genes in the mice at random to find other genes that could contribute to acute myeloid leukemia. They identified two other genes that work together with Npm1 to cause the disease. These genes affect cell growth and division and control the activity of genes in cells. Understanding the different processes leading to acute myeloid leukemia will help scientists to develop new medicines for the disease. - Nature Genetics, DOI: 10.1038/ng.796, 27 Mar 11

New Skin Cancer Gene, New Treatment

The discovery of a gene linked to skin cancer in zebrafish could lead to new treatments for the disease. The gene, called SETDB1, is thought to work alongside another known cancer causing gene called BRAF. Cancers formed from skin pigment cells, called melanomas, were previously linked to the BRAF gene in 2002. It was found that four fifths of human melanomas have a mutation in this gene. The BRAF gene causes skin pigment cells in the fish to become larger, darker and often cancerous. However, benign splotches can also have the BRAF mutation, suggesting the cancer is dependent on other genes as well. Screening more than 3000 fish, researchers found that the SETDB1 gene accelerates melanomas, causing them to grow sooner and faster. The gene was also found to be more active in two thirds of human melanomas. It is thought to release an enzyme that boosts the activity of other growth promoting genes linked to cancer. In a second study, researchers found combinations of over 100 genes that are linked to the development of melanomas. These genes are associated with stem cells called embryonic neural crest cells. It is thought that extra stem cells could lead to melanomas. Researchers were able to target these neural crest cells using an existing medicine for arthritis, called, leflunomide. Combining leflunomide with another medicine to reduce the activity of the BRAF gene, researchers were successful in treating melanomas in mice. The combination of medicines removed the tumor almost completely in two fifths of the mice. - Nature, DOI: 10.1038/nature09882, 24 Mar 11

Protein Linked to Autism in Mice

Research on GM mice has found how mutations in a single protein can lead to autism. The protein, called Shank3, regulates how nerve impulses are conducted between brain cells. Researchers bred GM mice that were unable to produce the Shank3 protein and observed their behavior. The mice were placed in a maze and the time spent in open/closed and light/dark parts of the maze was monitored. The level of social interaction of a mouse was also determined by whether it initiated contact with other mice in a social arena. Those mice missing the Shank3 protein were more anxious, displayed repetitive behavior and injured themselves while grooming. These mice also showed abnormal social interactions, tending to avoid other mice. This is similar to behavior in humans with autism, who often have communication deficits, impaired social interaction and repetitive behavior. Brain samples from the mice were also analyzed. Important proteins involved in the conduction of nerve impulses were missing in the mice lacking Shank3. The findings could lead scientists to new therapies for autism. The Shank3 protein is produced by a gene, also called Shank3. While autism has been linked to a mutation in the Shank-3 gene, only a small fraction of people with autism have this mutation. The Shank3 gene is one of many thought to contribute to autism spectrum disorders. - Nature, DOI: 10.1038/nature09965, 20 Mar 11

GM Pig Gets Cystic Fibrosis

A GM pig that gets cystic fibrosis is helping scientists understand the causes of the disease. The pig strain can also be used to test new therapies for CF. While the gene mutation that causes cystic fibrosis has been known for over 20 years, it is still unclear exactly how this mutation results in the condition. In humans, thick sticky mucus accumulates in the lungs and digestive tract. Patients have difficulty breathing and digesting food and suffer frequent lung infections. The CF gene mutation affects the production of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). CFTR forms a channel in cells that helps maintain salt and water balance in cell membranes. Researchers discovered that in the GM pig most of the CFTR protein is misprocessed. Only a small amount of the protein gets to the cell membrane where it is needed. If researchers can understand why it is misprocessed then they could direct treatments to transport more of the protein to the cell membrane. The GM pig has similar symptoms to CF in humans and the CFTR protein behaves in the same way as in humans. Researchers hope to use the model to test new treatments for cystic fibrosis. - Science Translational Medicine, DOI: 10.1126/scitranslmed.3001868, 16 Mar 11

Mouse Mimics Another Childhood Brain Cancer

Scientists have created a mouse model of the most common type of pediatric brain cancer. The model has furthered understanding of the cause of the cancer and can be used to test potential therapies. Pilocytic astrocytoma (PA) is a slow growing tumor that develops in children and young adults. The tumor is diffuse and so it is often difficult for surgeons to completely remove it. Further treatment is then needed to remove the remaining cancer tissue. Chemotherapy and radiation therapy are often ineffective at removing the remaining cancerous tissue so new treatments are needed. The new mouse model will help direct and test such treatments. Scientists created the mouse model using a defective version of a gene called BRAF. Defects in BRAF have previously been linked to the development of pilocytic astrocytomas and it is found in more than half of all pilocytic astrocytoma cases. Researchers put the defective BRAF gene into a virus and transferred it to the neuronal precursor cells of mice. Neuronal precursor cells are the starting cells from which neurons develop. Nine tenths of mice injected with the defective gene developed brain cancer. The tumors had the same growth characteristics and tissue structure as pilocytic astrocytoma. The research shows that the single gene defect in BRAF is a significant cause of pilocytic astrocytoma. The researchers found that the BRAF gene defect causes a cellular signaling pathway, which in healthy cells is active only in case of acute need, to be permanently activated. Medicines have been developed to try and inhibit the activity of this pathway and so stop cancer growth. Researchers tested one of these medicines, called sorafenib, on the new mouse model. It was found to slow the growth of tumors in the mice. - Journal of Clinical Investigation, 10.1172/JCI44656, 14 Mar 11

RatCAP Brain Scanner

Scientists have developed a mini brain-scanner that allows them to study brain function and behavior simultaneously in rats. The new device, called the RatCAP, will further understanding of neurological conditions, such as Alzheimer's, Parkinson's and epilepsy. The RatCAP uses a tiny positron emission tomography (PET) scanner. Usually PET can only be used on anesthetized rats, because they don't keep still long enough to be scanned. But the new portable device can image rats' brains while they are conscious, allowing researchers to examine behavior and brain function at the same time. The RatCAP is tiny compared to conventional PET scanners, weighing just 250g. The device is supported against the rat's head using a combination of springs and motion stabilizers. PET uses radioactive tracers to watch how different chemicals are metabolized in the body. Weakly radioactive chemicals are injected into the animal and result in the emission of high-energy light. From this, a ring of detectors in the PET scanner can determine the location and concentration of the chemical. Using the RatCAP, researchers measured levels of the neurotransmitter dopamine in active rats. Dopamine has many functions in the brain, many of which influence behavior, movement and memory. A lack of dopamine in the brain is associated with Parkinson's disease. The researchers compared the levels of dopamine to those in anaesthetized rats. Dopamine is usually associated with excitement and reward and so levels were expected to be higher in the conscious rats. But, surprisingly, the levels were higher in the anaesthetized rats, suggesting that anesthesia may influence dopamine uptake. The finding has important implications for existing research involving PET scanners, which had assumed observations under anesthesia would match those in conscious animals. The researchers also measured the activity of a rat from its body motions and number of head turns. This could then be matched minute-by-minute to dopamine levels in the brain. The more active the rat, the lower the dopamine levels. It is expected the RatCAP will have application in a wide range of behavioral studies using different neurotransmitters. However, the size of the device may not allow its use in behaviorally challenging experiments, such as nose-poking into small spaces for food rewards. - Nature Methods, DOI: 10.1038/nmeth.1582, 13 Mar 11

Poor Diet in Pregnancy Linked to Diabetes in Offspring

Poor diet during pregnancy could raise the risk of offspring developing diabetes, according to new research in rats. Rats fed a low protein diet produced offspring that were more likely to develop type-2 diabetes as they grew older. Researchers fed pregnant rats either a normal diet, containing two tenths protein, or a reduced protein diet, containing around one tenth protein. Both sets were given the same number of calories. Researchers then took pancreatic cells from the rats' offspring at three months and at 15 months old. The cells from offspring of poorly fed mothers had alterations in particular parts of their DNA. As the rats grew older, these changes became more pronounced. Researchers linked this effect to a chemical called HNF 4-alpha. The chemical is known to play an important role in glucose metabolism and the functioning of pancreatic cells. Offspring of rats fed a low protein diet had lower levels of HNF 4-alpha than those born to normally fed mothers. This decreases the ability of the pancreas to produce insulin and leads to early development of diabetes. HNF 4-alpha levels normally decrease with age, but the poor maternal diet speeds up these ageing effects in offspring. The alteration of gene activity by environmental factors, such as diet, is called an epigenetic effect. Epigenetic changes are more subtle that genetic mutations and can take years or even generations to have a noticeable effect. The same DNA region responsible for the development of diabetes in the mice was also present in human pancreatic cells. However, scientists caution that further research is needed to establish if a similar effect occurs from poor diet in humans. - Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1019007108, 8 Mar 11

Brain Cells Created in the Lab

Scientists have created neurons from embryonic stem cells. The neurons can be used to investigate the causes of Alzheimer's disease and to test for potential medicines. Researchers transplanted the neurons into the hippocampus region of the brain in mice. The hippocampus plays a significant role in memory function. They found that the neurons functioned normally, weaving themselves into the brain tissue. The neurons also began producing important neurotransmitters. Alzheimer's affects around half a million people in the UK. During the course of the disease, 'plaques' and 'tangles' develop in the structure of the brain, leading to the death of brain cells. Researchers produced a type of cell known as basal forebrain cholinergic neurons. These neurons are associated with memory function and their loss is thought to be important in the early stages of Alzheimer's. The new technique allows scientists to create a near limitless supply of these neurons for research. The research also raises the possibility of neuron transplants to treat the disorder. However, scientists caution that such treatments are a long way off. The stem cells which the neurons are made from could produce tumors in the brain. Patients would also have to take immunosuppressant medicines to stop their body rejecting the transplant. To avoid this problem, researchers are now investigating how to create neurons directly from a patient's skin cells. As these cells would be genetically matched to the patient they wouldn't be rejected. - Stem Cells, DOI:10.1002/stem.626, 4 Mar 11

Mouse Mimics Childhood Brain Cancer

Scientists have created the first mouse model of a deadly form of childhood brain cancer. The model will be used to further understanding of how the cancer forms and to test potential medicines. The position of the tumor, entwined inside the brain stem, makes DIPG a difficult cancer to study. No effective chemotherapy medicines exist and surgery is impossible as the cancer cells embed themselves in a region of the brain stem essential for life. Only one victim in 100 survives more than five years. Researchers cultured cells from the human cancer and implanted them into the brains of healthy mice. These cancer cells went on to from DIPG-like tumors in the mice. This animal model of the disease can now be used to further understand how the cancer forms and for testing therapies. Using the model, the researchers investigated a potential molecular signaling pathway, called the Hedgehog pathway, that could cause the cancer to grow. The Hedgehog pathway is already linked to several other types of brain tumor. Medicines that inhibit the Hedgehog pathway already exist. Researchers will now test these on the new DIPG cancer mouse model. - Proceedings of the National Academy of Sciences, 10.1073/pnas.1101657108, 1 Mar 11

Heart Regeneration in Newborn Mice

Newborn mice can regenerate their own heart tissue following heart damage. This is the first time the effect has been observed in mammals and could lead to new treatment for heart damage in humans. Zebrafish are renowned for their regenerative abilities. They can repair heart damage throughout their life by the replication of existing heart cells, called cardiomyocytes. But adult mammals can't repair heart damage. Though they can replace a small number of heart cells, it isn't enough to mend the damage caused by a heart attack. However, the new research suggests a similar regenerative capacity exists in newly born mice. Researchers removed 15% of muscle tissue from one of the heart's chambers in one-day-old mice. Three weeks later, the heart muscle tissue had been repaired. Researchers compared the heart-damaged mice to mice that had been given a dummy operation that didn't harm the heart. Two months later, heart scans showed the heart-damaged mice's hearts to be pumping as well as the test group. However, when the same procedure was performed on seven-day-old mice, there was no regeneration. Instead of regrowing heart tissue, there was heart failure. This suggests there is a narrow time window in mammals in which the heart loses its regenerative abilities. It seems mammals, as well as fish, have the ability for self-repair, but only for a short time after birth. As the development and early function of the mouse heart is similar to the human heart, researchers believe that a similar process could occur in humans. It is hoped that the research could lead to ways to restart the regenerative capacity of the heart in human adults. Such treatments would be vital in treating patients after a heart attack. Heart muscle cells are lost in a heart attack and the heart loses pump function. This can lead to heart failure and death. 750,000 people in Britain currently suffer from heart damage. Researchers are now looking for genes that could be linked to heart regeneration. They are also screening for medicines that could reawaken the mechanisms in adult hearts. - Science, 10.1126/science.1200708, 25 Feb 11

Exercise Reduces Aging in GM Mice

Regular endurance exercise reduces the effects of aging, according to new research on mice. Premature aging was prevented in mice running on a treadmill for 45 minutes, three times a week. Every tissue and organ examined, including the hair, skin, ovaries, testicles, spleen, kidneys, and liver, were healthier in mice that exercised compared to those living a sedentary lifestyle. Scientists genetically engineered the mice to age faster by creating a defect in a gene responsible for the mitochondria repair system. Mitochondria generate energy for the body's cells. It is thought that as mutations build up in the mitochondria DNA, they can no longer provide cells with enough energy. This stops the functioning of tissue and organs, leading to aging. In the non-exercising GM mice mitochondria malfunction much earlier in life, causing them to age prematurely before reaching one year. The sedentary mice were balding, graying, physically inactive, socially isolated and less fertile. However, at one year of age, none of the exercising GM mice had died. Exercising mice also looked as young as healthy non GM mice. Researchers examined the mitochondria of the exercising mice. They found fewer mutations and signs of damage. The findings suggest that endurance exercise improves mitochondrial function throughout the body. Other attempts to reduce the effects of aging have focused on 'exercise-pills' or changes in diet. The new research suggests that endurance exercise could be more effective - PNAS, 10.1073/pnas.1019581108, 22 Feb 11

New Understanding of 'Suspended Animation'

Research on bears has extended our understanding of large mammal hibernation. The findings pave the way to creating similar suspended animation states in humans, with important implications for medicine and long-haul space flights. Small mammals' body temperature plummets to near freezing temperatures during hibernation. But bears maintain a high body temperature during winter dormancy, leading some scientists to question whether bears actually hibernate. To test this, researchers observed American black bears in an Alaskan outdoor forest enclosure. During the period of winter dormancy the bears moved into isolated wooden nest boxes disguised to look like dens. In the nest boxes researchers were able to measure body temperature and metabolic activity, defined by the rate of oxygen consumption. The bears' metabolic rate dropped to a quarter of the normal rate, showing that bears do in fact hibernate. Researchers further found an unusual pattern of heat regulation. The bears' body temperature oscillated between a normal 36°C and a minimum of 30°C over a number of days. These fluctuations have never been seen before in hibernating animals. Smaller animals, such as mice and hedgehogs, experience repeated arousals during hibernation, during which their body temperature rises from near freezing back up to the normal 36°C. The research suggests that temperature doesn't play as important a role in reducing metabolic rate as previously thought. In smaller mammals, halving metabolic activity causes a 10°C fall in body temperature. But in the bears, when metabolic rate fell to a quarter of the normal level, body temperature only fell by 6°C. Researchers also measured heart, muscle and brain activity using implanted radio transmitters. They found the bears' heartbeat dropped from 55 to 14 beats per minute, but the rate varied depending on whether the bears were breathing at the time. After leaving hibernation, the bears kept a low metabolic rate for two to three weeks. This suggests there is a biochemical mechanism which suppresses metabolism in the bears. The exact mechanisms that underlie hibernation are still unknown but further understanding of these processes could one day enable scientists to induce similar suspended animation states in humans. Hibernation reduces energy costs in mammals and stops the losses in muscle, bone mass and function that normally occur over long periods of immobility and disuse. Such benefits could help astronauts survive lengthy space journeys. More usefully, inducing suspended animation in humans could be used to extend the medical 'golden hour' after a stroke or heart-attack, during which medical intervention is most effective. Further, manipulating these pathways could lead to new therapies for osteoporosis and muscle atrophy. - Science, 10.1126/science.1199435, 18 Feb 11

Wounds Trigger Tumors

Certain types of cancer could be triggered by simple wounds, according to new research on mice. Mice pre-disposed to a common type of skin cancer showed a significant increase in tumor development when given a small wound. Researchers pre-disposed the mice to cancer by causing a mutation in a gene with the potential to cause cancer, called an oncogene, in skin stem cells. The mutation itself didn't increase the rate of skin cancers, but when researchers cut a small disc of skin from the mice they developed skin cancer at the wound site. Even a cut as small as a paper cut increased the chances of a tumor forming. Lung, liver, bone and skin cancers have all been linked to wounds, but this is the first time research has uncovered a mechanism to explain the link. Skin stem cells normally stay near hair follicles in the lower skin layers. Here the mutated cells are kept in check by the body and tumors don't form. But wounds cause these cells to move to the surface to mend the damage. In doing so, the mutated stem cells alter a biochemical signaling pathway that is linked to skin cancer. Mutated skin stem cells can remain dormant in the lower skin layers for years, only becoming a threat afterwards, when a wound breaks the skin. - PNAS, 10.1073/pnas.1013098108, 14 Feb 11

Glowing Nerve Cells

Scientists have developed a way to make nerves glow in mice. The technique could help avoid accidental damage to nerves in surgery. Researchers injected fragments of fluorescent proteins into mice. The proteins preferentially bind to nerve tissue and so cause it to glow, making nerves stand out from the surrounding tissue. The protein even binds to nerves that have been damaged or severed, so long as they retain a blood supply. Surgeons usually identify nerves by their appearance and location to nearby tissue structures, but thin and buried nerves can be missed. The position and appearance of nerves can also be altered if nerves are invaded by a tumor or in areas of infection and injury. The new technique clearly alerts surgeons to nerves, helping to avoid accidental damage which can cause numbness, chronic pain and paralysis in patients. The fluorescent protein could also be used in surgery to repair injured nerves. The fluorescent effect occurs within two hours and lasts for up to eight hours. It has no lasting side-effects on the nerves. Researchers further tested the fluorescent proteins on human tissue, with similar results. They are now working towards human clinical trials. - Nature Biotechnology, 10.1038/nbt.1764, 6 Feb 11

Enzyme Linked to Blindness

Age-related macular degeneration (AMD) has been linked to the lack of a protective enzyme in the retina. The finding could lead to new treatments for the disease. AMD is one of the leading causes of blindness. The age related disease affects 500,000 people in the UK. One in 50 people over 50 years have the condition. In the 'dry' form of the disease light sensing rods and cones are damaged in the central part of the retina. This impacts on the central field of vision, causing a black spot to appear which grows progressively bigger. Sufferers can have difficultly reading, driving and recognizing people. Researchers found that an enzyme called DICER1 was less active in sufferers of dry AMD. They then turned off the gene that makes DICER1 in mice. They found the mouse retinal cells were damaged by the build-up of small pieces of genetic material called Alu RNA. The enzyme DICER1 plays an important role in destroying Alu RNA. Without the enzyme Alu RNA can't be controlled and can build up to harmful levels. Researchers are now trying to identify molecules that could increase levels of the DICER1 enzyme, or stop the build-up of Alu RNA. - Nature,10.1038/nature09830, 6 Feb 11

HIV-like Virus Cured in Mice

Scientists have used a hormone to completely remove a HIV like virus from mice. When researchers gave the hormone, called IL-7, to mice it boosted their immune response to the virus. Regular doses of the hormone completely cleared the infection from the mice. The immune system is not normally able to destroy the HIV virus. This is because the HIV virus replicates within the T cells that are part of the immune system. Every day, HIV destroys billions of CD4+ T cells in a person infected with HIV, eventually overwhelming the immune system's capacity to regenerate or fight other infections. Patients are faced with incurable, lifelong infections. An estimated 86,500 Britons are living with HIV. The IL-7 hormone turns off a gene called SOCS-3 which becomes highly active when the body is overrun by infections such as HIV. The gene suppresses the body's immune response to prevent an over-reaction that can damage body tissue. However, in HIV the brakes are put on the immune system too early and the virus is able to persist. Using the hormone researchers were able to boost the immune system's killer T Cells, which seek out and kill infections, but without causing an over-reaction. Normal retro-viral drugs given to HIV patients prevent the virus replicating in the main body systems. But there are hidden inactive reserves of the virus which they can't remove. As soon as therapy is stopped these virus stores re-infect the body. It is thought the new treatment could be used to clear the inactive pockets of the virus as well, completely removing HIV from the body. Therapies will try to find ways to turn off the SOCS-3 gene for short periods of time to activate killer T cells to fight the viral infection. The technique could be applied to other infectious diseases, such as hepatitis B and C and tuberculosis. - Cell, 10.1016/j.cell.2011.01.011, 3 Feb 11

Type 1 Diabetes Treated in Mice

Type 1 diabetes has been treated in GM mice using antibodies. Researchers tested the treatment using an innovative mouse model that mimics the human form of type 1 diabetes. The model was created by introducing human genes into the mice. Many medicines found to work in the rodent version of type 1 diabetes are ineffective in human trials. The new mouse model increases the chance of success when moving from animal to human trials. Type 1 diabetes, also known as juvenile diabetes, affects people of any age. It is caused by the immune system attacking the insulin-producing cells in the pancreas. Without insulin the body is unable to regulate blood glucose levels and so patients must take daily insulin-injections. If not properly regulated, sufferers can face complications due to irregular blood sugar levels. Low blood sugar levels can lead to seizures and unconsciousness. High blood sugar can cause long-term damage to organs such as the heart and kidneys. The antibody, called anti-CD3, was able to stop the immune system attacking insulin producing cells in the mouse model. The antibody removes the cells that destroy the insulin producing cells. The antibody is now undergoing human clinical trials. - Science Translational Medicine, 10.1126/scitranslmed.3001830, 2 Feb 11

Artificial Blood Vessel Success in Animals

Artificial blood vessels for use in heart bypass surgery have been successfully tested in baboons and dogs. The artificial vessels were made using smooth muscle cells grown on tubular scaffolding. As the smooth muscle cells grow they secrete collagen, an important structural protein found in the walls of blood vessels. The artificial vessels can be stored for up to a year, making them readily available, and can be used by any patient. Researchers can already grow blood vessels using a patient's own cells, but the process takes several months and so this is usually too long to wait before surgery. The number of heart bypass operations in the UK is more than 28,000 per year. Surgery is needed to 'bypass' the blocked arteries which bring oxygen to the heart muscle. Coronary heart disease is the UK's biggest killer. Usually blood vessels taken from another part of the patient's body are used to bypass the blocked arteries. But sometimes it's not possible to use a patient's own blood vessels and a synthetic one is used instead. However, these can easily become clogged as a result of immune responses. The new artificial vessels do not have this problem. After six months use in dogs and monkeys there was no evidence of clogging or thickening, suggesting they could be used for long term transplantation. Moreover, the blood vessels were able to change shape in response to blood flow and were colonized by cells from the patient's own body that make up natural blood vessels. Producing the artificial blood vessels has several stages. A few weeks after the artificial blood vessels are grown the scaffolding degrades, leaving the collagen and smooth muscle behind. However, this can't be transplanted into patients if it contains 'foreign' smooth muscle cells because it would cause an immune reaction. To overcome this, researchers washed away the smooth muscle with detergent. This leaves behind only the supportive collagen tube, which can't cause an immune reaction. The resulting blood vessel can be used by any patient, removing the need for custom made vessels. The same method could potentially be used to construct other bodily tissue, such as skin, ligaments or cartilage. In these tissues it is the structure, not the cells, that is most important. It is hoped human trials will begin using the artificial blood vessels next year. - Science Translational Medicine, 10.1126/scitranslmed.3001426, 2 Feb 11

Protein Predicts Cancer Spread

Scientists have identified a protein that tumors make when they are likely to spread. By halting the production of the compound, researchers were able to stop the spread of tumors in mice. The protein, called CPE-delta N, is normally used in the body to process insulin and other hormones. But researchers also found it in high levels in cancers that had spread through the body. The spreading of cancer cells to other parts of the body is called metastasis. Cancers cells break away from the primary tumor and travel to other parts of the body through lymph and blood vessels. Metastatic cancer has a high chance of killing patients. Researchers transplanted metastatic liver cancer cells beneath the skin of mice. In half the tumors they stopped the production of CPE-delta N by a method called antisense. Antisense blocked the activity of the genes used to produce CPE-delta N. Tumors that didn't produce CPE-delta N were much smaller than normal liver tumors. Researchers then implanted these liver tumors into the livers of another group of mice. After a month, only the untreated tumors had spread to other parts of the body. Researchers are now trying to find a method to stop the production of CPE-delta in tumors already growing in the body. The protein could also be used to predict if a cancer tumor is likely to spread in patients. Researchers analyzed cancer tissue in 99 patients with liver cancer. They compared the amount of CPE-delta N in the tumor to the amount in surrounding tissue. They found tumors were much more likely to return or spread if CPE-delta N levels in the tumor were more than twice that in the surrounding tissue. Using this test, researchers were able to predict that tumors would spread or return in patients with nine tenths accuracy. They also predicted that tumors would not return in patients with 75% accuracy. Patients with high CPE-delta N levels could be given extra chemotherapy to control the risk of spread. - Journal of Clinical Investigation, 10.1172/JCI40433, 1 Feb 11

Gut Bacteria Affect Brain Development

Bacteria in the gut acquired early in life could affect future brain development and behavior, according to new research on mice. Researchers compared behavior and gene expression in mice raised with normal microorganisms to those that were 'germ-free'. The germ-free mice were more active and engaged in riskier activities than the normal mice. Brain transmitters that play an important role in learning and memory also behaved differently in the two groups of mice. Similarly, the levels of proteins involved in communication in the central nervous system were different. Gut bacteria colonize their hosts during pregnancy or shortly after birth. They play an important role in the health of the developing organism. Gut bacteria have been linked to the development of the liver, digestive tissue and blood vessels. Other harmful bacteria have been linked to neurological disorders such as autism and schizophrenia. Researchers tested the differences in exploratory behavior between normal mice and germ-free mice. They placed the mice in a light-dark box and a maze with elevated levels. Germ-free mice were found to spend more time in the light and in elevated areas, suggesting riskier behavior and lower anxiety than normal mice. The results suggest that the bacteria acquired early in life could contribute to psychiatric conditions. Germ-free mice were also infected with normal gut bacteria shortly after birth. They displayed similar behavior to normal mice, suggesting that bacteria introduced early in life can still affect brain development. Future research hopes to determine exactly which bacteria affect brain development and how they communicate with the brain. - PNAS, 10.1073/pnas.1010529108, 31 Jan 11

Lack of Omega-3 Linked to Mood Disorders

Mice fed a diet lacking in the fatty acid omega-3 are more susceptible to mood disorders, according to new research. Symptoms of depression were displayed by mice fed an omega-3 deficient diet. They explored less and stayed nearer the cage wall than those fed a normal diet, indicating anxious behavior. Omega-3 deficient mice also gave up sooner on a swimming test. Omega-3 has previously been liked to mood disorders, but the underlying mechanism remained unknown. The new research was able to pin this mechanism down. It was found that the functioning of important brain receptors that regulate pain and appetite decrease in omega-3 deficient mice. Mice fed an omega-3 deficient diet also had lower levels of certain beneficial fatty acids in their brains, but higher levels of the harmful fatty acid omega-6. Humans and mice cannot make omega-3 on its own and so depends on dietary sources. But even in the developed world many people often still lack enough omega-3 in their diet. Dietary supplements that counteract this have had some success in treating depression in humans. However, the effect is small and not all patients with depression lack omega-3. So lack of omega-3 is only one of many contributing factors to mood disorders. However, the simplicity of dietary supplements makes them a valuable potential treatment. - Nature Neuroscience, 10.1038/nn.2736, 30 Jan 11

Cancer Medicine Could Treat Spinal Injury

The cancer medicine Taxol has been used to treat spinal injury in rats. Taxol was found to stimulate nerve growth and reduce scarring after spinal injury. Spinal injuries can cause long term damage as injured nerve cells in the central nervous system don't re-grow. The nerve cell's cytoskeleton, which acts like a supportive scaffolding, becomes unstable in injured cells. This stops the structured re-growth of cells. Damaged tissue also becomes replaced by scar tissue, which creates a barrier for growing nerve cells. Taxol can reduce both of these obstacles to regeneration. The cancer medicine stabilizes the ‘scaffolding' of the nerve cells so that they regain their ability to re-grow. Taxol also enables growing nerve cells to cross the scar tissue barrier. Scar tissue still forms at the site of the injury, and so is still able to carry out its protective role. Researchers injected Taxol into the spinal injury site in rats using a miniature pump. The rats' ability to walk was tested a few weeks later by making them balance on sticks. Normally rats perform well in this task, but those with spinal injury misstep and slide through the sticks. Rats treated with Taxol did better in this task. Taxol was given to the rats directly after spinal injury. But it is unknown if the medicine will have an effect if given weeks or months after a spinal injury. In addition, the effects of Taxol may not be strong enough to treat spinal injury on its own. The medicine may need to be used in combination with other treatments. Taxol is normally given in chemotherapy treatments in much larger doses to kill cancer cells and reduce their ability to divide, but this causes significant side effects. It is thought the small, localized doses needed to treat spinal injury will have far fewer side effects. - Science, 10.1126/science.1201148, 27 Jan 11

Hormone Improves Memory in Rats

A hormone has been found that boosts the memory of an unpleasant experience in rats. The findings could lead to treatments that enhance memory formation. Understanding how memories form and are strengthened is critical to cognitive enhancement therapies for diseases such as Alzheimer's. Researchers gave rats a memory of an unpleasant experience. They placed the rats in a box that was half light and half dark. When the rats moved into the dark side of the box they were given a small electric shock to the feet. This created a memory reminding the rats not to go into the dark area. Researchers found a hormone called IGF-II increased in their brains after the fear memory had formed. Researchers then injected the hormone, which is similar to insulin, into the rats' brains. This boosted the rats' memory of the foot shock. They wouldn't venture into the dark area for up to three weeks after the initial memory was formed. However, the hormone was found to be ineffective if given more than a day after the initial experience. Researchers were also able to block the increase in IGF-II when the memory was formed. This stopped the formation of the memory so that the rats still ventured into the dark area. As the study only considered memories that involve fear it is unclear whether IGF-II can boost memories in sufferers of Alzheimer's disease or dementia. - Nature, 10.1038/nature09667, 26 Jan 11

Kidney Regenerator Cell Identified

Zebrafish are renowned in the science community for their ability to repair damage to heart muscle. Now scientists have identified a cell in zebrafish that regenerates the kidneys. The finding could lead to new treatments for kidney failure in humans. Kidney failure is common in humans as we are unable to generate new nephrons. Nephrons are the basic functional cells of kidneys. They are responsible for regulating concentration and filtering out waste products from the blood. Though humans can partly repair nephrons, shortly before birth they stop being able to form new ones. Fish, however, are able to keep generating nephrons throughout their lives, producing new ones after kidney damage. Researchers transplanted progenitor kidney cells — similar to stem cells — to other zebrafish. They were able to track the nephrons produced by these progenitor cells using fluorescent proteins. They found the transplanted progenitor cells produced new nephrons in the host fish, acting in a similar way to stem cells. Critically, the new nephrons were integrated into the fish's blood supply. The nephron generation mechanism in the fish resembled that in growing human embryos. This suggests that human kidneys could contain similar nephron progenitors, but they are dormant. Understanding how nephron progenitors work in zebrafish could lead to methods to activate or artificially engineer similar nephron progenitors in humans. Such treatments will become increasingly important as kidney failure levels rise in line with rising levels of diabetes and hypertension. - Nature, 10.1038/nature09669, 26 Jan 11

Spinal Cord Damage Bridged in Rats

Artificial ‘scaffolding' has been used to bridge spinal cord injuries in rats. Rats treated with the technique recovered movement in their hind legs. It is hoped the technique could be used to treat patients with paraplegia. Scar tissue and fluid filled cysts form at the site of spinal cord injury and interfere with the healing process. But the newly developed biodegradable scaffolding provides tiny channels so that nerve tissue can bypass this region. The hollow fibers are made from biodegradable plastic half a millimeter in diameter. The scaffolding is coated with molecules that help cells to secure themselves along the tube. It is then filled with a gel that stimulates nerve repair and growth. Researchers placed the tubes in regions of spinal cord damage in rats. After six months they found nerve fibers had grown through the channels, along with supporting cells needed for nerves to survive. Rats treated with the artificial fibers recovered some movement in their hind legs. Those that weren't treated remained paralyzed. It is unclear whether the nerve fibers growing through the tubes were connecting up with the spinal cord on the other side. It is important that this occurs if spinal injury is to be fully treated. - ACS Nano, 10.1021/nn102461w, 25 Jan 11

Fighting Cancer with Cancer

An innovative new approach to fighting cancer has reduced tumor size in mice. The treatment is currently undergoing human trials. Researchers designed 'cancer beads' that encapsulated tumor cells from humans in a sugar called agrose. When implanted in the abdomen of mice with cancer, the cancer beads reduced tumor size by between three tenths and six tenths. Fighting cancer using other cancer cells may appear contradictory, but researchers believe the cancer cells in the beads are producing proteins that inhibit tumor growth. As a tumor grows, cancer cells further inside the tumor reach a point where they are surrounded by similar cancerous cells and so stop growing. It is thought that the encapsulated cancer cells secrete proteins which cause the tumor to think it is surrounded by similar cancer cells and so stop it growing. Other proteins secreted by the cancer beads are thought to promote cell death and reduce the ability to form new blood vessels, which the cancer needs to survive. Researchers also tested the cancer beads on pet dogs and cats. The beads appeared to extend the lifespan of the animals and in some cases almost removed the tumor. The survival time of one group of 11 dogs was increased by three times that normally expected. There was no control group to compare the results with (the animals had not responded to conventional treatment) so the pets were undergoing the experimental treatment. Researchers are now putting encapsulated mouse tumor cells into human patients with advanced colon, pancreatic and prostate cancers. Tumors from one species do not grow in other species and so the procedure is thought to be safe. Between 500 and 750 beads about the size of pea are put into the abdomen of patients. Researchers hope to present data on the human trials later this year. - Cancer Research, 10.1158/0008-5472, 24 Jan 11

RNA Based Medicine for HIV

A potential RNA based treatment for HIV is showing positive results in tests on mice. Researchers injected the two component medicine into GM mice engineered to be susceptible to HIV. They found the quantity of the HIV virus in the mouse's blood fell significantly. The medicine is composed of two different types of RNA. The first, called an aptamer, binds onto a protein on the surface of the HIV virus and neutralizes it in the blood. The aptamer also transports the second type of RNA, called small interfering RNA (siRNA) into infected cells. siRNA then blocks the expression of two genes in infected cells that HIV needs to replicate. When mice were given just the aptamer component of the medicine, levels of virus in the blood were also found to fall. However, the combination of aptamer and siRNA medicine suppressed the virus for a week longer than just the aptamer. siRNA was also directly found inside target cells and reduced the expression of the two genes HIV needs for replication. However, there remain questions over how widespread the uptake of siRNA into infected cells is. Patients would need regular injections of the medicine as it is only effective for about a week. The new medicine could help patients who have developed resistance to other HIV drugs. - Science Translational Medicine, 10.1126/scitranslmed.3001581, 19 Jan 11

MicroRNA Combats Prostate Cancer

Small strands of RNA, called microRNA, inhibit prostate cancer stem cells in mice. Researchers found that microRNA can suppress a surface protein often found on prostate cancer stem cells and so inhibit the action of the cell. Cancer stem cells are linked to tumor recurrence and the spread of cancer to other organs. They are also more resistant to treatment than other cancer cells. Many cancer stem cells are known to carry a specific protein on their surface called CD44. Researchers found that those cells expressing high levels of the CD44 cancer protein had reduced levels of the microRNA miR-34a. They then tried to target this protein using miR-34a. miR-34a was found to reduce tumors in cell cultures containing prostate cancer stem cells with CD44. The researchers then transplanted human prostrate cancer cells into mice. They found prostate tumors in mice receiving miR-34a treatment were one third to half the average size of those in control group mice. Injections of miR-34a also reduced the spread of cancer to the lungs in one tumor type. Although microRNAs provide a potential new treatment for prostate cancer, delivering microRNAs to the right place in the body is difficult. Medicines companies are now working on this challenge. - Nature Medicine, 10.1038/nm.2284, 16 Jan 11

Tiny Camera Reveals Brain Changes in Real Time

An innovative new instrument has been developed that enables scientists to observe changes deep inside the brains of animals. The micro-endoscope allows scientists to watch nerve cells and blood vessels in animal brains over an extended period of time. Previously, observing inner parts of the brain involved highly invasive surgery and the area of interest could only be looked at once. The new technique enables researchers to look at the same point in the brain many times over days or even weeks. Observing changes over time will help scientists track the progression of many slowly evolving diseases. For example, the micro-endoscope could watch the damaging changes to nerve connections that are the hallmark of some neurodegenerative diseases. Similarly, the progression of tumor growth and the effectiveness of medicines could be observed with the new instrument. The tip of the micro-endoscope is 500 to 1000 micrometers in diameter (a micrometer is one millionth of a meter). A glass tube is inserted into the animal's brain to guide the tip to the region of interest. When inserted, the micro-endoscope can take images of the area. After imaging the micro-endoscope is removed and the animal can be returned to its cage. Days or weeks later the instrument can be reinserted to take more pictures of the same area. The new device has already been used by researchers to explore the structure of neurons in a region of the brain called the hippocampus. The hippocampus is situated deep in the brain and plays an important role in the formation of memories. It was thought the structure of neurons in the region would change with the formation of new memories. But surprisingly the researchers found no change. The growth of tumor cells in the brains of mice has also been observed with the instrument. Scientists were able to watch how blood vessels in the brain changed as the tumor grew. This allows scientists to study changes over time without sacrificing animals to see changes at specific time intervals. - Nature Medicine, 10.1038/sj.nm.2292, 16 Jan 11

GM Chickens Prevent Transmission of Bird Flu

Bird flu epidemics could be prevented by GM chickens that stop the spread of flu to other birds. Scientists modified the chickens to produce small 'decoy' molecules that interfere with virus reproduction. Chickens can act as 'bridging hosts' that allow new strains of flu to be transmitted to humans. The GM chickens could prevent this, reducing the chance of human flu epidemics. The findings could also improve food security and the welfare of chickens by bringing bird flu epidemics under control. Flu viruses spread inside a host by reproducing themselves. To do this they must replicate their genetic information using a replicating enzyme. The researchers interfered with this process in chickens by introducing a new gene that produces a small 'decoy' molecule. The decoy tricks the replicating enzyme to bind to it rather than the virus's genetic material, so stops the virus reproducing. Researchers infected 10 GM chickens and 10 non-GM chickens with bird flu. They then exposed half of each set to both GM and non-GM chickens. All non-GM chickens infected with flu died within five days, as did all chickens they were in contact with. The GM chickens also died after a few days, but they did not pass the infection onto any other chickens. So although the GM chickens can catch flu, they cannot pass it onto to other chickens. The decoy molecule mimics part of the flu virus that is the same for all types of influenza A, and so prevents transmission of many strains of flu. Influenza A was responsible for the recent swine flu and bird flu epidemics as well at the infamous 1918 Spanish flu outbreak. Conventional poultry flu vaccines, on the other hand, only protect against very closely matching strains of flu. As flu viruses constantly evolve this requires the regular development of new vaccines and widespread revaccination programs. GM chickens may provide more protection against evolving flu strains than attempts to vaccinate poultry. - Science, 10.1126/science.1198020, 14 Jan 11

Enzyme Reduces Cancer Spread

The spread of cancer to other organs has been reduced in mice by blocking an enzyme. Researchers blocked the enzyme LOXL2 in mice using chemicals and genetic engineering techniques. While this did not slow the rate of the tumor growth, it did reduce the spread of the cancer to the liver and lungs. The findings could lead to the development of medicines that stop the spread of cancer to other organs. The enzyme could also be used to test whether cancer is likely to spread in patients and so predict patient outcomes. The spread of cancer to other parts of the body, called metastasis, is responsible for nine tenths of cancer deaths. Around 47,000 new cases of breast cancer are diagnosed in the UK each year and around 12,000 patients die from the disease. Analyzing tissue samples from patients with breast cancer, researchers found that high levels of the enzyme LOXL2 were linked to cancer spread and poor survival rates. Researchers injected mice with two different types of breast cancer cells which then grew into tumors. One cell type produced high levels of LOXL2, while the other had been genetically modified to inhibit production of LOXL2. They found that tumors grew at a similar rate in mice regardless of the level of LOXL2 in the injected cancer cells. This suggests that LOXL2 is not required for tumor growth. However, mice injected with tumor cells with low levels of LOXL2 had fewer secondary tumors in the lung or liver. Researchers found that LOXL2 helps cancer cells to invade surrounding tissue by controlling levels of molecules called TIMP1 and MMP9. These molecules have previously been shown to play a role in metastasis. Researchers also genetically modified mice to produce breast tumors early on in their life. After four weeks, they injected the mice with a chemical called D-penicillamine, which inhibits LOXL2. There was no difference in tumor size between mice that had been injected with D-penicillamine and those which had not. However, those treated with the chemical had fewer secondary lung tumors. Delaying treatment with D-penicillamine until five weeks resulted in no difference in the number of secondary lung tumors. This suggests that LOXL2 is only important in the early stages of metastasis. - Cancer Research, 10.1158/0008-5472.CAN-10-2868, 13 Jan 11

Rats Sniff out Tuberculosis

Gambian pouched rats are being used by scientists to sniff out tuberculosis in mucus samples. The new method could provide a quick and cheap way to detect the disease in the developing world. The rats are trained from an early age to detect the tuberculosis bacteria amongst the many other bacteria in the human body. Trainers put positive and negative mucus samples under ‘sniffing holes'. They are rewarded with peanuts and bananas for spending longer at positive tuberculosis samples and so learn to sniff only at these samples. The training process takes about six months. Modern machine tests for tuberculosis are very expensive. The alternative is smear microscopy, in which dyed samples must be examined under the microscope for the presence of tuberculosis bacteria. But the bacteria can only be picked up if there is a high concentration. This causes many positive cases to go undetected. Researchers compared the detection sensitivity of smear microscopy to Gambian pouched rats. Analyzing 10,523 samples using a microscope they detected 1,403 that contained the disease. Rats sniffing the same samples detected tuberculosis in nine tenths of samples identified as positive using a microscope. But the rats detected a further 1,418 positive samples missed by the microscope. Many of these were later confirmed by closer microscope analysis to be positive. While the rats display noteworthy detection abilities and are much cheaper than alternative methods, scientists caution that the results are only preliminary. It is unclear whether the rats must be periodically retrained or what effects the rats' environment could have on their detection abilities. - The American Journal of Tropical Medicine and Hygiene, 10.4269/ajtmh.2010.10-0180, 5 Jan 11

Vaccine Induces Cocaine Immunity in Mice

Cocaine immunity has been induced in mice using an altered version of the common cold virus. The vaccine could be used to break cocaine addiction in humans. The vaccine contained in the virus trains the body's defenses to see cocaine molecules as intruders, and so the immune system destroys the cocaine molecules before they can reach the brain. Researchers hooked modified cocaine molecules onto an adenovirus. They also discarded the components of the virus that cause sickness, leaving only those that cause an immune response. When injected into mice, the virus caused the immune system to produce antibodies to cocaine. Antibody production is part of the body's natural response to potentially harmful bacteria and viruses. When these antibodies were put in a test tube with cocaine molecules they were found to engulf the cocaine. The vaccine had trained the antibodies to see cocaine molecules as intruders. As the immune response destroys the drug before it reaches the brain's pleasure center, it is hoped the vaccine could help those addicted to cocaine to kick the habit. The effects of the vaccine in mice last for at least 13 weeks. Researchers also tested the effect of the vaccine on mouse behavior. Those given the vaccine were much less hyperactive when on cocaine than those not vaccinated. It is hoped the vaccine will quickly move into human trials. Similar vaccines could be developed against addictions to nicotine, heroin and other opiates. - Molecular Therapy, 10.1038/mt.2010.280, 4 Jan 11

 

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