FST-344

Follistatin Research and Muscle Growth

Myostatin is a protein produced by muscle cells themselves that inhibits muscle cell growth and differentiation. It is a member of the TGF-beta protein family and therefore is susceptible to inhibition by follistatin. Previous research has shown that animals lacking myostatin have significantly more muscle mass and are stronger than normal. This led scientists to speculate that administration of follistatin could improve muscle growth and help to treat a number of medical conditions, like muscular dystrophy, that impact muscle growth and strength. In mouse models, follistatin has been shown to increase lean muscle mass without the need for special dietary or exercise requirements. After just eight weeks of follistatin injections, mice in the treatment group had 10% more muscle mass than mice in the control group^[1]. This, again, is a result obtained without exercising the mice or subjecting them to special diets, indicating that gains could be even more substantial with appropriate training. Research in everything from mice to monkeys has shown increased muscle size and strength when follistatin therapy is initiated. There is hope that the protein can be used to treat muscle disorders, such as inclusion body myositis, that have so far proved relatively resistant to pharmacologic intervention^[2]. Research in mouse models of Duchenne muscle dystrophy (DMD), for instance, show that follistatin treatment leads to hypertrophy of skeletal muscle while also reducing inflammation and fibrosis. The benefits are dose-dependent and lead to clinically relevant changes in strength in the setting of DMD^[3]. These are significant findings that could help doctors to reduce or eliminate the weakness associated with certain muscle disorders, thereby restoring quality of life and reducing morbidity in these conditions. One interesting aspect of research into the effects of follistatin on muscle growth has found that gene administration of follistatin at any age can lead to long-term benefits on muscle hypertrophy. In mouse models, one-time administration of follistatin via gene therapy has led to more than two years of enhanced mass and strength in both normal and dystrophic animals. These benefits were observed regardless of the age of the animal at the time of gene therapy^[4]. Research indicates that follistatin boosts muscle growth by stimulating the insulin/IGF-1 pathway. Interestingly, the protein only requires that one of these signaling molecules be present for full anabolic effect. Follistatin actually causes a decrease in muscle expression of IGF-1, something that was initially counter-intuitive to scientists until they understood that its effects can also be mediated via insulin itself^[5]. Research indicates that follistatin influences the pancreas to produce more insulin, suggesting that the protein is intimately associated with insulin signaling.