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Gene therapy reverses genetic mutation responsible for heart failure in muscular dystrophy

that the treatment would be effective. However, we never imagined it would be so effective, particularly in protecting against or reversing the damage to the heart caused by this mutation and extending lifespan," explained Dr. Tong Zhu, M.D., Ph.D., a research associate in the department of orthopaedic surgery and the first author of the study. "In fact, if this study holds up in human clinical trials, it may have profound implications for the treatment of heart failure."

Dr. Xiao cautioned, however, that human clinical trials of this therapy face several major challenges. Foremost is that effective treatment requires the injection of a large amount of the virus so there is enough to reach every muscle cell. Because 30 percent to 40 percent of the population has antibodies to human AAVs, there is always the possibility that the effectiveness of this form of gene therapy may be blunted by a host immune response. However, Dr. Xiao is optimistic that will not be the case.

"The AAV-8 we used in this study was isolated from monkeys, so we are very hopeful it will be able to deliver the genes before the human immune system produces antibodies to block it. In addition, we used a muscle-specific promoter in the virus, which also should lower the risk of any potential immune response against the gene product. In fact, in hamsters, we did not find any immune response to the human delta-sarcoglycan protein that was encoded by the AAV vector under the control of this promoter," he explained.

In addition to Drs. Xiao and Zhu, other authors of this study are: Liqiao Zhou, V.M.D.; Zhong Wang, M.D., Ph.D.; Chunping Qiao, M.D., Ph.D.; Chunlian Chen, M.D.; and Juan Li, M.D., Molecular Therapy Laboratory, department of orthopaedic surgery, and Satsuki Mori, M.D., and Charles McTiernan, Ph.D., Cardiovascular Institute, all from the University of Pittsburgh School of Medicine; and Daowen Wang, M.D., Ph.D., department of cardiology, Tongi Hospital, Huazhong Scie
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Source:University of Pittsburgh Medical Center


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