FDA Grants Orphan Drug Designation to Treatment for Facioscapulohumeral Muscular Dystrophy

GBC0905, a small-molecule drug, suppresses DUX4 function and protects skeletal muscle cells from muscle fiber death. Amanda Rickard, lead scientist of Genea Biocells’ FSHD program, said in a statement that the company expects the drug to be curative.

Genea Biocells has announced that the FDA has granted GBC0905, for the treatment of facioscapulohumeral muscular dystrophy (FSHD), an Orphan Drug Designation.

FSHD, which affects between 4 and 10 per 100,000 people, is caused by the abnormal expression of the DUX4 gene, which allows the DUX4 protein to be produced in cells and tissues where it is not typically present. Expression of the protein causes muscle weakness and atrophy that typically affects muscles in the face, shoulder girdle, and upper arms, though it can also affect muscles of the abdominal wall, hip, and thigh.

GBC0905, a small-molecule drug, suppresses DUX4 function and protects skeletal muscle cells from muscle fiber death. Amanda Rickard, lead scientist of Genea Biocells’ FSHD program, said in a statement that the company expects the drug to be curative.

If GBC0905 is eventually approved, it will expand the options available for patients with FSHD; current treatment for FSHD is generally directed to treating individual patients’ symptoms, including surgery to help stabilize the scapulae, physical therapy to help maintain muscle flexibility and manage pain, or the use of adaptive aids or assistive devices.

Research recently published in Molecular Therapy demonstrated the feasibility of using such small-molecule drugs to inhibit DUX4.1 The authors of the study hypothesized that multiple epigenetic pathways might be deregulated in FSHD monocytes, with multiple potential targets for therapeutic manipulation.

They determined that knocking down any of several epigenetic regulators—which have wide-ranging roles—in FSHD myocytes could decrease the expression of the full-length isoform of DUX4, and that even a modest inhibition of certain pathways leads to substantially reduced levels of DUX4. The ability to modulate the levels of DUX4 without completely eradicating expression of its upstream regulators, which play important cellular roles, wrote the authors, “is particularly encouraging for the development of targeted therapies.”

Reference

Himeda CL, Jones TI, Virbasius CM, Zhu LJ, Green MR, Jones PL. Identification of epigenetic regulators of DUX4-fl for targeted therapy of facioscapulohumeral muscular dystrophy [published online April 25, 2018]. Mol Ther. doi: 10.1016/j.ymthe.2018.04.019.