Preventing muscle atrophy with gene therapy and anabolic growth factors

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Curr Opin Clin Nutr Metab Care. 2006 May;9(3):207-13.

Gene therapy with anabolic growth factors to prevent muscle atrophy.

Schakman O, Thissen JP.

Department of Diabetology and Nutrition, Catholic University of Louvain,

Brussels, Belgium.

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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