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Archive - Apr 2012

April 10th

Gene Could Play Key Role in Preventing Pathology in Deadly Pulmonary Fibrosis

An international team of researchers led by Georgia State University (GSU) scientists has found a key component in the pathological process of pulmonary fibrosis, a fatal disease for which there is currently no cure. The scientists found that a key human gene, CLYD, serves as a crucial negative regulator in the development of the disease, halting its progression that leads to death. The research was published online on April 10, 2012 in the journal Nature Communications. "In some patients, CLYD does not function as it should or its protein level is lower than in normal individuals," said Dr. Jian-Dong Li, director of the GSU Center for Inflammation, Immunity, and Infection (CIII) and Georgia Research Alliance (GRA) Eminent Scholar in Inflammation and Immunity. "If this does happen, the human tissue-repairing response can go out of control, leading to the development of fibrosis," added Dr. Li, senior author of the study and professor of biology at GSU. According to the American Lung Association, about 140,000 Americans have been diagnosed with the disease. Patients' breathing symptoms worsen over time, and many patients live only three to five years after diagnosis. There are currently no effective medicines available to health care professionals to cure pulmonary fibrosis. Professionals can treat the symptoms to reduce inflammation using steroids and immunosuppressants, but there are serious side effects over time, including immune system suppression, which makes patients even more susceptible to infections. "The disease often develops after infection or injury. In the case of infections brought on by Streptococcus pneumoniae, a form of pneumonia, the body's immune system responds and tries to repair the damage, but in the case of fibrosis, this repairing process is overactive and causes scarring of the lungs," said Dr.

April 5th

Stem Cell Work Permits Production of Unlimited Quantities of Cystic Fibrosis Lung Tissue for Drug Testing

Harvard stem cell researchers at Massachusetts General Hospital (MGH) have taken a critical step in perhaps making possible the discovery, in the relatively near future, of a drug to control cystic fibrosis (CF), a fatal lung disease that claims about 500 lives each year, with 1,000 new cases diagnosed annually. Beginning with the skin cells of patients with CF, Jayaraj Rajagopal, M.D., and colleagues first created induced pluripotent stem (iPS) cells, and then used those cells to create human disease-specific functioning lung epithelium, the tissue that lines the airways and is the site of the most lethal aspect of CF, where the mutant genes cause irreversible lung disease and inexorable respiratory failure. That tissue, which researchers can now grow in unlimited quantities in the laboratory, contains the delta-508 mutation, the mutation responsible for about 70 percent of all CF cases and 90 percent of the ones in the United States. The tissue also contains the G551D mutation, a mutation that is involved in about 2 percent of CF cases and the one cause of the disease for which there is now a drug. The work is featured on the cover of the April 6, 2012 issue of Cell Stem Cell. Postdoctoral fellow Hongmei Mou, Ph.D., is first author on the paper, and Dr. Rajagopal is the senior author. Dr. Mou credits learning the underlying developmental biology in mice as the key to making tremendous progress in only two years. "I was able to apply these lessons to the iPS cell systems," she said. "I was pleasantly surprised the research went so fast, and it makes me excited to think important things are within reach.

Spontaneous Mutations Linked to Autism Risk with Older Dads

Researchers have turned up a new clue to the workings of a possible environmental factor in autism spectrum disorders (ASDs): fathers were four times more likely than mothers to transmit tiny, spontaneous mutations to their children with the disorders. Moreover, the number of such transmitted genetic changes increased with paternal age. The discovery may help to explain earlier evidence linking autism risk to older fathers. The results are among several from a trio of new studies, supported in part by the National Institutes of Health, finding that such sequence changes in parts of genes that code for proteins play a significant role in ASDs. One of the studies determined that having such mutations boosts a child's risk of developing autism 5 to 20 fold. Taken together, the three studies represent the largest effort of its kind, drawing upon samples from 549 families to maximize statistical power. The results reveal sporadic mutations widely distributed across the genome, sometimes conferring risk and sometimes not. While the changes identified don't account for most cases of illness, they are providing clues to the biology of what are likely multiple syndromes along the autism spectrum. "These results confirm that it's not necessarily the size of a genetic anomaly that confers risk, but its location – specifically in biochemical pathways involved in brain development and neural connections. Ultimately, it's this kind of knowledge that will yield potential targets for new treatments," explained Thomas R. Insel, M.D., director of the NIH's National Institute of Mental Health (NIMH), which funded one of the studies and fostered development of the Autism Sequencing Consortium, of which all three groups are members.

April 3rd

Why Cancer Drug Causes Diabetes-Like Symptoms in Some

Scientists at Dana-Farber Cancer Institute have discovered why diabetes-like symptoms develop in some patients given rapamycin, an immune-suppressant drug that also has shown anti-cancer activity and may even slow ageing. Rapamycin is widely used to prevent organ rejection and is being tested as a cancer treatment in clinical trials. About 15 percent of patients, however, develop insulin resistance and glucose intolerance after taking the drug; until now, scientists had not identified the reason. In a study published in the April 4, 2012 issue of Cell Metabolism, the researchers report that normal mice given rapamycin were more likely to have trouble regulating their blood sugar because of a drop in insulin signaling, which was triggered by activity of a protein called Yin Yang 1, or YY1. But animals in which the YY1 protein was "knocked out" in their muscles had no such response to rapamycin – they were protected against the development of diabetes-like symptoms. This result pinpointed YY1 as the target of rapamycin responsible for the loss of normal insulin function. One of the finding's implications is that physicians should consider giving anti-diabetes drugs along with rapamycin, says Pere Puigserver, Ph.D., senior author of the report. The results also raise a caution flag for researchers and non-scientists who are excited about the potential for rapamycin to extend life, based on recent studies in animals including mammals, he notes. "The possibility of increased diabetes risk needs to be taken into account" in further research on the anti-ageing properties of rapamycin and related compounds, says Dr. Puigserver. Rapamycin is a drug derived from bacteria found on Easter Island, and was approved in 1999 by the FDA as an immunosuppressant in transplant patients.