In April, the FSH Society awarded Julie Dumonceaux PhD, or University College London, Institute of Child Health. a grant of $9,659.43 for one year for a project aimed at better understanding patients’ response to a class of drugs called myostatin inhibitors.
These drugs, such as Acceleron’s ACE-083 which is currently in a clinical trial in FSH muscular dystrophy patients, target myostatin, a molecule that the body produces naturally to inhibit muscle growth. The rationale for blocking myostatin is to enable muscle to achieve greater mass than it otherwise would. In conditions such as FSHD, where muscle mass is lost, a myostatin inhibitor would in theory enable muscle to re-grow without having to fight an uphill battle against the growth-blocking effects of myostatin.
“Muscle wasting is one of the biggest challenges in neuromuscular disorders,” writes Dr. Dumonceaux in the summary of her FSH Society grant proposal. “Myostatin being a negative regulator of muscle mass, its down-regulation has been seen as a promising tool to counterbalance this muscle wasting and at least 6 anti-myostatin molecules have been developed by pharmaceutical companies. However, so far, the clinical trials have been very disappointing and clinical endpoints have been barely reached. These results are surprising since during the phase 1 trials on healthy volunteers, an improvement of muscle mass was observed.”
Dr. Dumonceaux has shown that in “neuromuscular patients (including FSHD patients), the circulating myostatin levels are very low in the most atrophying diseases such as Duchenne Muscular Dystrophy. In less atrophying disease such as FSHD, as less pronounced modification of the myostatin pathway is observed. Similar results were obtained in muscle biopsies. This is very important since one could have thought that because myostatin is mainly produced by the muscle tissue, the reduction of circulating myostatin levels could have been the direct consequence of this muscle loss.” Dr. Dumonceaux suggests “another mechanism: in neuromuscular diseases, an atrophy is observed and the muscle tissue tries to counterbalance this atrophy by inhibiting the myostatin pathway in order to increase, or at least not reduce, the muscle mass. We have observed a correlation between atrophy and the reduction of myostatin and observed that under a myostatin threshold, an antimyostatin approach does not work. Finally, regarding our results, the most important question is probably: is it useful to develop anti-myostatin drugs? The answer might be yes, but patient stratification, based on myostatin and/or follistatin circulating levels might be useful to predict patient eligibility” for clinical trials.
The funding provided by the FSH Society will help us to finish performing the experiments which may be of importance for neuromuscular patients, and FSHD patients in particular, and may deeply impact future and current clinical trials using myostatin inhibitors.”
Read more about grants funded by the FSH Society here.