Extraordinary Measures – Many shots on goal

by Jamshid Arjomand, Chief Science Officer

With a dozen or more potential FSHD therapies in the drug development pipeline, why is the FSHD Society continuing to invest substantial funds− a record $2 million this year− in grants for more basic research? The most recently funded projects include investigations into the structure and function of SMCHD1 (the gene associated with FSHD Type 2); defective muscle cell membrane repair in FSHD; the role of metabolic changes, reactive oxygen species, and hypoxia (lack of oxygen) in FSHD; what happens after the DUX4 gene is expressed to damage muscle; and interactions between the immune system and muscles in FSHD. There’s also funding going into better understanding the workings of losmapimod (Fulcrum Therapeutic’s candidate FSHD drug).

If the linchpin in FSHD is the DUX4 gene, why not focus on stopping DUX4? Indeed, that’s what all of the drugs that are currently getting close to clinical trials are aiming to do. One could flip around the question asked above and inquire instead: why are there so many similar tactics?

One answer to the first question is that trying to stop DUX4 might not be enough by itself. A drug might not shut DUX4 down completely. Or DUX4 may have effects that propagate long after it has left the scene. Or it may turn out that it’s important to block something that happens earlier in the disease process. And because FSHD symptoms appear to be the result of diverse biochemical events that happen at different stages of the disease, diverse drugs may be needed to be deployed against these different processes. Many researchers working on FSHD therapies believe that effective treatments may require a cocktail of drugs tailored to the individual patient.

For the same reason that each patient is different, and not all drugs are created equal, it is a sign of a healthy drug development ecosystem to see several companies pursuing complementary strategies. We believe that it will benefit patients to have options rather than just a single, one-size-fits-all treatment. That’s why it’s so important to keep pushing the frontiers of knowledge to gain a deeper insight into the disease process and help identify alternative mechanisms for potential treatments.

Twice a year, the FSHD Society solicits high-quality grant proposals, assembles our scientific advisory board in hours-long discussions to review and rank each proposal, negotiates contracts with each institution and tracks the progress of each project. We ask each researcher to put in their best effort to help identify the next possible point of intervention, so there may be another shot on goal – another chance for a therapy for FSHD. None of this would be possible without the extraordinary measures by our community to support their work.