Myotubular Myopathy
This orphan disease is a primary target for 4s3 Bioscience. Myotubular myopathy is an X-linked genetic disorder which affects approximately 1 in 50,000 newborn males, characterized by severe muscle weakness and hypotonia at, or soon after birth. Death from respiratory failure occurs in the most severe cases in the first weeks of life, and much of the remaining population within the first year. A small minority of patients has less aggressive mutations and survives into childhood or longer, but require respiratory assistance and are wheelchair bound. Most patients with MTM are identified in the first few weeks of life as “floppy” babies – confirmation is by genetic testing and the characteristic appearance of severely reduced myocyte size with numerous centrally placed nuclei on a muscle biopsy. MTM1, the affected protein, is a 3-phosphatase acting on the substrate phosphoinositide PtdIns(3)P. Distribution of MTM1 is ubiquitous, but the pathophysiology of the disease occurs primarily in skeletal muscle. In preclinical studies, we have demonstrated that our 3E10Fv-MTM1 conjugate, 4s3-001, has efficacy as an enzyme-replacement product candidate. A manuscript containing data from this study is currently in preparation for publication and IND-enabling manufacturing & preclinical studies have been initiated.