Gene therapy with anabolic growth factors to prevent muscle atrophy

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Abstract

Purpose of review

Many situations cause muscle atrophy. When severe, muscle atrophy is associated with an increase in morbidity and mortality. This loss of muscle mass is thought to be due to an imbalance between catabolic and anabolic pathways, resulting in an increase of muscle protein proteolysis and in a decrease in protein synthesis. Changes in muscle levels of muscle growth factors are thought to play a major role in this imbalance. Despite recent better understanding of the metabolic and molecular derangements leading to muscle wasting, therapy of muscle atrophy still has a poor success rate.

Recent findings

The recent demonstration that changes in local growth factors, such as insulin-like growth factor-I and myostatin, occur during muscle atrophy has stimulated research interest to prevent muscle mass loss by delivering these growth factors or their inhibitors into the muscle. During the last few years, several advances in the field of muscle gene transfer, using electroporation or recombinant adeno-associated viral vectors, have opened novel therapeutic ways to deliver growth factors able to counteract the loss of muscle mass.

Summary

Preventing decrease of insulin-like growth factor-I muscle, or inhibiting myostatin action by local genes over-expression, may provide a clinically relevant avenue for the preservation, attenuation or reversal of disease-related muscle loss.

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