Individuals with PWS have motor difficulties throughout life, with low muscle tone and decreased muscle mass. Growth hormone therapy is helpful in increasing muscle mass, but it does not completely normalize body composition. It would be helpful to achieve normal muscle mass in those PWS since muscle is important not only for maintaining strength and endurance, but also because it is a metabolically active tissue. Appropriate muscle mass is important to properly regulate glucose and lipid levels in the body. Thus, efforts to develop pharmacological interventions that help build muscle mass may have relevance to PWS. Most of these interventions are currently being developed for serious disorders that affect muscle structure (the muscular dystrophies, for example) or for muscle wasting diseases. However, if proven safe and effective, it might be reasonable to evaluate whether these drugs have clinical application in PWS.
The biological processes that control muscle formation have become much more clear in recent years. Myostatin is a molecule produced by the body to regulate muscle mass, sending a ‘stop growing’ signal to the muscle. A few rare individuals (and some very muscular cows and dogs) have been described with a deficiency of myostatin, and they end up with approximately double the normal muscle mass. Pharmaceutical companies have been working on inhibitors of myostatin, reasoning that such molecules should also function to increase muscle mass. Investigations in this area have also identified other regulators of muscle mass, and in some cases, these look to be more promising therapeutic targets. One of these is the ‘activin type IIB receptor’. A recent study demonstrated that a synthetic form of this protein, administered to mice, resulted in significant increases in muscle mass [ Cadena et al, 2010 ]. This potentially therapeutic molecule, named ACE-031, has been developed by Acceleron Pharma Inc. Recently, the company has completed small clinical trials in healthy adults, reporting that single or multiple doses of ACE-031 were safe and resulted in increased muscle volume and lean body mass. Clinical trials in patients Duchenne muscular dystrophy (DMD) are now underway, and the drug has just received “Fast Track” designation from the FDA. The FDA Fast Track initiative seeks to accelerate the clinical evaluation, review and approval process for promising drugs aimed at treating life-threatening illnesses.
It’s great to see a potential new therapy for DMD. The PWS community will be following the continued development of this drug with considerable interest.