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Archive - 2011

July 16th

New Gene Mutation Discovered for Familial Parkinson’s Disease

Researchers have discovered a new gene mutation they say causes Parkinson's disease. The mutation was identified in a large Swiss family with Parkinson's disease, using advanced DNA sequencing technology. The study, published July 15, 2011, in the American Journal of Human Genetics, was led by neuroscientists at the Mayo Clinic campus in Florida and included collaborators from the U.S., Canada, Europe, United Kingdom, Asia, and the Middle East. "This finding provides an exciting new direction for Parkinson's disease research," says co-author Dr. Zbigniew Wszolek, a Mayo Clinic neuroscientist. "Every new gene we discover for Parkinson's disease opens up new ways to understand this complex disease, as well as potential ways of clinically managing it." The team found that mutation in VPS35, a protein responsible for recycling other proteins within cells, caused Parkinson's disease in the Swiss family. Mutated VPS35 may impair the ability of a cell to recycle proteins as needed, which could lead to the kind of errant buildup of protein seen in some Parkinson's disease brains and in other diseases like Alzheimer's disease, says co-author Dr. Owen Ross, a neuroscientist at Mayo Clinic in Florida. "In fact, expression of this gene has been shown to be reduced in Alzheimer's disease, and faulty recycling of proteins within cells has been linked to other neurodegenerative diseases," he says. So far, mutations in six genes have been linked to familial forms of Parkinson's disease, with many mutations identified as a direct result of Mayo Clinic's collaborative research efforts. Dr. Wszolek has built a worldwide network of Parkinson's disease investigators, many of whom have conducted research at Mayo Clinic. The study's first author, Dr. Carles Vilariño-Güell, and the senior investigator, Dr.

Scientists Discover New Role for Vitamin C in Retina, Posssibly Brain

Nerve cells in the eye require vitamin C in order to function properly — a surprising discovery that may mean vitamin C is required elsewhere in the brain for its proper functioning, according to a study by scientists at Oregon Health & Science University, and collaborators, published in the June 29, 2011 issue of the Journal of Neuroscience. "We found that cells in the retina need to be 'bathed' in relatively high doses of vitamin C, inside and out, to function properly," said Dr. Henrique von Gersdorff, a senior scientist at OHSU's Vollum Institute and a co-author of the study. "Because the retina is part of the central nervous system, this suggests there's likely an important role for vitamin C throughout our brains, to a degree we had not realized before." The brain has special receptors, called GABA-type receptors, that help modulate the rapid communication between cells in the brain. GABA receptors in the brain act as an inhibitory "brake" on excitatory neurons in the brain. The OHSU researchers found that these GABA-type receptors in the retinal cells stopped functioning properly when vitamin C was removed. Because retinal cells are a kind of very accessible brain cell, it's likely that GABA receptors elsewhere in the brain also require vitamin C to function properly, Dr. von Gersdorff said. And because vitamin C is a major natural antioxidant, it may be that it essentially 'preserves' the receptors and cells from premature breakdown, Dr. von Gersdorff said. The function of vitamin C in the brain is not well understood. In fact, when the human body is deprived of vitamin C, the vitamin stays in the brain longer than anyplace else in the body. "Perhaps the brain is the last place you want to lose vitamin C," Dr. von Gersdorff said.

July 8th

Discovery May Lead to New Treatment for Malignant Glioma

Cleveland Clinic researchers have identified a cellular pathway that cancer stem cells use to promote tumor growth in malignant glioma, an aggressive brain tumor. The research – published in the July 8, 2011 issue of Cell – also found that existing medications block this cancer-promoting pathway and delay glioma growth in animal models, suggesting a new treatment option for these often fatal brain tumors. Malignant gliomas account for more than half of the 35,000-plus primary malignant brain tumors diagnosed each year in the United States. Unfortunately, the outlook for patients with malignant gliomas is poor. For patients with the most severe, aggressive form of malignant glioma (grade IV glioma or glioblastoma multiforme), median survival is 9 to 15 months with the best available therapies. These treatments include surgery followed by radiation therapy with the chemotherapy temozolomide followed by additional temozolomide treatment. Although differences in tumors between people were known to exist, researchers have only recently begun to understand the importance of differences between cancer cells within the same patient. Groups of cells within a glioma which promote brain tumor formation in animal models – called cancer stem cells – have been identified. These cancer stem cells are often resistant to radiation and chemotherapy, making them an important target for developing new and effective disease treatments. In the recently published manuscript, a team of Cleveland Clinic researchers – led by Dr. Jeremy Rich, Chairman, and Dr. Anita Hjelmeland, of the Department of Stem Cell Biology and Regenerative Medicine of the Lerner Research Institute of Cleveland Clinic – define a novel molecular pathway that cancer stem cells use to promote tumor growth.

July 4th

Scientists Sequence Genome of Long-Lived, Cancer-Resistant Naked Mole-Rat

The naked mole-rat is native to the deserts of East Africa and has unique physical traits that allow it to survive in harsh environments for many years. It has a lack of pain sensation in its skin and has a low metabolic rate that allows it to live underground with limited oxygen supply. For the first time, scientists from the University of Liverpool and The Genome Analysis Centre (TGAC) in Norwich, UK, have sequenced the genome of the naked mole-rat to understand its longevity and resistance to diseases of aging. Researchers will use the genomic information to study the mechanisms thought to protect against the causes of aging, such as DNA repair and genes associated with these processes. To date, cancer has not been detected in the naked mole-rat. Recent studies have suggested that its cells possess anti-tumor capabilities that are not present in other rodents or in humans. Researchers at Liverpool are analyzing the genomic data and making it available to researchers in health sciences, providing information that could be relevant to studies in human aging and cancer. Dr. Joao Pedro Magalhaes, from the University of Liverpool's Institute of Integrative Biology, said: "The naked mole-rat has fascinated scientists for many years, but it wasn't until a few years ago that we discovered that it could live for such a long period of time. It is not much bigger than a mouse, which normally lives up to four years, and yet this particular underground rodent lives for three decades in good health. It is an interesting example of how much we still have to learn about the mechanisms of aging. We aim to use the naked mole-rat genome to understand the level of resistance it has to disease, particularly cancer, as this might give us more clues as to why some animals and humans are more prone to disease than others.

July 2nd

New Treatment Strategy for Usher Syndrome

Usher syndrome is the most common form of combined congenital deafness-blindness in humans and affects 1 in 6,000 of the population. It is a recessive inherited disease that is both clinically and genetically heterogeneous. In the most severe cases, patients are born deaf and begin to suffer from a degeneration of the retina in puberty, ultimately resulting in complete blindness. These patients experience major problems in their day-to-day lives. While hearing loss can be compensated for with hearing aids and cochlea implants, it has not proven possible to develop a treatment for the associated sight loss to date. Researchers at Johannes Gutenberg University Mainz (JGU) in Germany have now developed a new treatment approach to this disease. In previously conducted research into this subject, the research team headed by Professor Uwe Wolfrum of the Institute of Zoology at Mainz University had already gained insight into some of the fundamental molecular processes and mechanisms causing this debilitating syndrome. Using the results of this successful basic research, the Usher treatment team in Mainz headed by Dr. Kerstin Nagel-Wolfrum has now evaluated potential ocular treatment options. Their attention was focused on a mutation identified in a specific German family known to develop the most severe form of Usher syndrome. This mutation is a so-called nonsense mutation in the USH1C gene, which leads to the generation of a stop signal in a DNA sequence, resulting in premature termination of protein synthesis. The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal Human Gene Therapy.

July 1st

New Class of Anti-Angiogenesis Drugs Identified

Massachusetts General Hospital (MGH) researchers and colleagues have discovered the first of an entirely new class of anti-angiogenesis drugs – agents that interfere with the development of blood vessels. In a June 27, 2011 report in Proceedings of the National Academy of Sciences/Early Edition, the investigators describe how a compound derived from a South American tree was able, through a novel mechanism, to interfere with blood vessel formation in animal models of normal development, wound healing, and tumor growth. "Most of the FDA-approved anti-angiogenesis drugs inhibit the pathway controlled by vascular endothelial growth factor or VEGF, which directly stimulates blood vessel development," says Dr. Igor Garkavtsev, of the Steele Laboratory for Tumor Biology at MGH, lead author of the study. "Although these drugs have become standard treatments for several types of cancer, they only provide modest benefit in terms of extending patient survival, so more effective drugs targeting tumor vasculature are needed." While tumors need to generate and maintain their own blood supply to keep growing, tumor vasculature tends to be highly disorganized, which interferes with the effectiveness of traditional treatments like radiation and chemotherapy. Drugs that target the VEGF pathway can "normalize" tumor vasculature and improve the effectiveness of other therapies, but in addition to their limited effect on patient survival, such agents also can generate resistance or have toxic effects. In their search for drugs that block blood vessel growth in different ways, Dr. Garkavtsev and his colleagues focused on pathways involved with the adhesion of endothelial cells that line blood vessels to the outer vessel wall.

June 19th

PKD1 Gene Controls Development of Multiple Forms of Polycystic Disease

A single gene is central in the development of several forms of polycystic kidney and liver disease, Yale School of Medicine researchers report online on June 19, 2011, in Nature Genetics. The findings suggest manipulating activity of PKD1, the gene causing the most common form of polycystic kidney disease, may prove beneficial in reducing cysts in both liver and kidney. "We found that these conditions are not the result of an all or nothing phenomenon," said Dr. Stefan Somlo, the C.N.H. Long Professor of Medicine and Genetics and Chief, Section of Nephrology and senior author of the study. "The less PKD1 is expressed, the more cysts develop. Conversely, expressing more PKD1 can slow the process." The most common form of this condition is called autosomal dominant polycystic kidney disease (ADPKD), a condition passed on to children from one parent affected with the disease that is found in 600,000 people in the United States alone. Two genes, PKD1 and PKD2, are responsible for the onset of this condition. PKD patients also develop cysts of the liver and Somlo and colleagues had previously identified families with identical cysts found only in the liver. They found two different genes were responsible for this related condition. The researchers wanted to know how liver-only polycystic disease was related to ADPKD. In a series of experiments using both genetically engineered mouse models and biochemical studies, they found that the activity of only one of the four genes, PKD1, controlled cyst formation in the other forms of the disease. Experiments in mice showed that modulating dosage of PKD1 could slow disease progression.

June 15th

Whole-Genome Sequencing IDs Disease, Suggests Treatment for Afflicted Twins

When Noah and Alexis Beery were diagnosed with cerebral palsy at age two, their parents thought they at last had an answer to the problems that had plagued their twin infants from birth. However, that proved only a way station on a journey to find an answer to the children's problems that combined their mother's determination, the high tech world of next-generation sequencing in the Baylor Human Genome Sequencing Center, and the efforts of talented physicians from across the country. In a report in the June 15, 2011 issue of Science Translational Medicine, researchers from Baylor College of Medicine, experts in San Diego and at the University of Michigan in Ann Arbor describe how the sequencing of the children's whole genome along with that of their older brother and their parents zeroed in on the gene that caused the children's genetic disorder, which enabled physicians to fine-tune the treatment of their disorder. More than that, it also took human genome sequencing to a new level – that of improving treatment for an individual. The Baylor Genome Sequencing Center has pioneered whole genome sequencing of individuals, beginning when they presented Nobel Laureate Dr. James Watson with his full genome sequence on May 31, 2007. It was followed up in 2010, when Dr. Richard Gibbs, director of the Baylor Human Genome Sequencing Center, and Dr. James Lupski, vice chair of molecular and human genetics at BCM, published information on Lupski's whole genome sequence, identifying the gene mutation that caused his form of Charcot-Marie-Tooth Syndrome, an inherited disorder. "When the Baylor HGSC sequenced Watson's genome, it showed we could do a whole genome sequence," said Dr. Lupski. "When we sequenced my genome, it showed that whole genome sequencing was robust enough to find a disease gene among the millions of genetic variations.

Drug Helps Glucose Control in Type 1 Diabetics on Insulin

Results of a small, observational study conducted at the University at Buffalo suggest that liraglutide, an injectable medication used to treat type 2 diabetes, also helps type 1 diabetics on insulin achieve optimal control of their blood glucose levels. If the findings are confirmed in a larger, prospective, randomized study now being planned by the UB researchers, they could mean the first significant, new treatment for type 1 diabetes since insulin was discovered and made available in the 1920s. The research has been published online ahead of print in the European Journal of Endocrinology. It also was recently presented at the annual meeting of the Endocrine Society in Boston, where it received recognition as one of the most outstanding abstracts presented and the best in the field of diabetes. "Since the development of injectable insulin, there has been nothing definitive in terms of a significant advance in type 1 diabetes treatments," says Dr. Paresh Dandona, UB distinguished professor of medicine in the School of Medicine and Biomedical Sciences and senior author on the study. "That is the tragedy of the type 1 diabetic. This study shows that liraglutide can provide even well-controlled type 1 diabetics with additional benefits that help them achieve even better blood glucose levels," says Dr. Dandona. The patients on liraglutide, which is marketed as Victoza, also saw a reduction in appetite and food intake and the paper reports that body weight significantly fell in patients who took the drug for 24 weeks. The unfunded study was a retrospective analysis of data. It was conducted at Kaleida Health's Diabetes-Endocrinology Center of Western New York, which Dr. Dandona directs. At the start of the study, all 14 patients had hemoglobin A1C levels of under 7, which is considered optimal.

June 13th

Deadly Amphibian Disease Reaches Last Disease-Free Region in Central America

Smithsonian scientists have confirmed that chytridiomycosis, a rapidly spreading amphibian disease, has reached a site near Panama's Darien region. This was the last area in the entire mountainous neotropics to be free of the disease. This is troubling news for the Panama Amphibian Rescue and Conservation Project, a consortium of nine U.S. and Panamanian institutions that aims to rescue 20 species of frogs in imminent danger of extinction. Chytridiomycosis has been linked to dramatic population declines or even extinctions of amphibian species worldwide. Within five months of arriving at El Cope in western Panama, chytridiomychosis extirpated 50 percent of the frog species and 80 percent of individuals. "We would like to save all of the species in the Darien, but there isn't time to do that now," said Dr. Brian Gratwicke, biologist at the Smithsonian Conservation Biology Institute and international coordinator for the Panama Amphibian Rescue and Conservation Project. "Our project is one of a few to take an active stance against the probable extinction of these species. We have already succeeded in breeding three species in captivity. Time may be running out, but we are looking for more resources to take advantage of the time that remains." The Darien National Park is a World Heritage site and represents one of Central America's largest remaining wilderness areas. In 2007, Dr. Doug Woodhams, a research associate at the Smithsonian Tropical Research Institute, tested 49 frogs at a site bordering the Darien. At that time, none tested positive for the disease. In January 2010, however, Dr. Woodhams found that 2 percent of the 93 frogs he tested were infected. "Finding chytridiomycosis on frogs at a site bordering the Darien happened much sooner than anyone predicted," Dr.