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Gene Therapy Overcomes Heart Failure In Muscular Dystrophy

Researchers at the University of Pittsburgh have successfully treated heart failure in an animal model that is genetically //prone to develop a human muscular dystrophy. The article detailing this study is published in the Oct. 25 edition of the journal Circulation. The authors say that this is the first time that a gene therapy has been used in a therapeutic way.

Lead author, Xiao Xiao, Ph.D., associate professor of orthopedic surgery at the University of Pittsburgh School of Medicine said that attempts to treat the muscle with genes directed at it have been successful because of inherent characteristics of the muscle itself, 'Previous attempts at systemic gene therapy for muscle have not been very effective because blood vessel capillaries act much like a mosquito net, blocking the gene drugs from reaching the muscle cells. Fortunately, we found a virus that is just small and sneaky enough to get through this net and deliver the therapeutic gene to both skeletal and cardiac muscle cells,' he said.

The virus that was successfully used to deliver the gene to the muscle is named the adeno-associated virus, or AAV, a class of relatively small viruses that do not cause any known disease. Dr Xiao and his team used the AAV-8, which can penetrate the capillary net and thus can be effective in whole body treatments. The team tested this therapy against limb girdle muscular dystrophy, or LGMD. In humans, this condition leads to severe damage and weakness to muscles, particularly around the hips and shoulders and the heart. Naturally, the lifespan is shortened owing to cardiac and respiratory failure. The injection of a high dose of AAV-8 was accompanied by significant improvements in the skeletal and cardiac muscle tones in the affected hamsters. After eight months of gene therapy, the hamsters were found to have completely normal hearts. The untreated LGMD animals died of heart failure or other complications of muscular dystrophy by 37 weeks, while the t
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