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. Multiple types of gene therapy are in the preclinical stage of development for the treatment of FSHD. Antisense therapy utilizes antisense oligonucleotides that bind to DUX4 messenger RNA, inducing its degradation and preventing DUX4 protein production. Phosphorodiamidate morpholinos, an oligonucleotide modified to increase its stability, have been shown to selectively reduce DUX4 and its effects; however, these antisense nucleotides have poor ability to penetrate muscle. MicroRNAs (miRNAs) directed against DUX4, delivered by viral vectors, have shown to reduce DUX4, protect against muscle pathology, and prevent loss of grip strength in mouse FSHD models. Arrowhead pharmaceuticals is developing an RNA interference therapeutic against DUX4, named ARO-DUX4, and intends to file for regulatory clearance in third quarter of 2021 to begin clinical trials. Genome editing, the permanent alteration of genetic code, is being researched. One study tried to use CRISPER-Cas9 to knockout the polyadenylation signal in lab dish models, but was unable to show therapeutic results. Potential drug targets Inhibition of the hyaluronic acid (HA) pathway is a potential therapy. One study found that many DUX4-induced molecular pathologies are mediated by HA signaling, and inhibition of HA biosynthesis with 4-methylumbelliferone