Spanning multiple countries in Europe, it has launched the European Trial Network. Notable cases
Chip Wilson is a Canadian billionaire and founder of Lululemon. He has pledged 100 million Candian dollars to research through the venture Solve FSHD. Chris Carrino is the radio voice of the Brooklyn Nets. He founded the Chris Carrino Foundation for FSHD, oriented towards research funding. Morgan Hoffman is an American professional golfer. He started the Morgan Hoffman Foundation, oriented towards research funding. Research directions
Pharmaceutical development
After achieving consensus on FSHD pathophysiology in 2014, researchers proposed four approaches for therapeutic intervention:
enhance the epigenetic repression of the D4Z4
target the DUX4 mRNA, including altering splicing or polyadenylation;
block the activity of the DUX4 protein
inhibit the DUX4-induced process, or processes, that leads to pathology.Small molecule drugs
Most drugs used in medicine are "small molecule drugs," as opposed to biologic medical products that include proteins, vaccines, and nucleic acids. Small molecule drugs can typically be taken by ingestion, rather than injection. Losmapimod, a selective inhibitor of p38α/β mitogen-activated protein kinases, was identified by Fulcrum Therapeutics as a potent suppressor of DUX4 in vitro. Results of a phase IIb clinical trial, revealed in June 2021, showed statistically significant slowing of muscle function deterioration. Further trials are pending. Casein kinase 1 (CK1) inhibition has been identified by Facio Therapies, a Dutch pharmaceutical company, to repress DUX4 expression and is in preclinical development. Facio Therapies claims that CK1 inhibition leaves myotube fusion intact, unlike BET inhibitors, p38 MAPK inhibitors, and β2 agonists.Gene therapy
Gene therapy is the administration of nucleotides to treat disease.
Not rarely do both contribute to disease in the same individual.In those with FSHD2, although they have do not have a 4qA allele with D4Z4 repeat number less than 11, they still often have one less than 17 (relatively short compared to the general population), suggesting that a large number of D4Z4 repeats can prevent the effects of an SMCHD1 mutation. Further studies need to be done to determine the upper limit of D4Z4 repeats in which FSHD2 can occur.In those with a 4qA allele and 10 or fewer repeats, an additional SMCHD1 mutation has shown to worsen disease, classifying them as both FSHD1 and FSHD2. In these FSHD1/FSHD2 individuals, the methylation pattern of the D4Z4 repeat array resembles that seen in FSHD2. This combined FSHD1/FSHD2 presentation is most common in those with 9 - 10 repeats, and is seldom found in those with 8 or less repeats. The relative abundance of SMCHD1 mutations in the 9 - 10 repeat group is likely because a sizable portion of the general population has 9 - 10 repeats with no disease, yet with the additive effect of an SMCHD1 mutation, symptoms develop and a diagnosis is made.