DEX-M74 for GNE Myopathy

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GNE myopathy is a rare adult-onset muscular disorder characterized by progressive muscle weakness, resulting in severe incapacitation within 10 to 20 years after onset. GNE myopathy is a genetic disorder that has been traced to mutations in the GNE gene. GNE encodes an enzyme that catalyzes the first two steps in the biosynthesis of sialic acid (SA). The subsequent deficiency of SA production is presumed to cause decreased sialylation of muscle glycoproteins, resulting in muscle degeneration. Recent studies have implicated the SA precursor N-acetyl-D-mannosamine (ManNAc, or DEX-M74) as a potential therapeutic agent for the treatment of GNE myopathy. The National Human Genome Research Institute at the National Institutes of Health (NIH) filed a patent application on the use of ManNAc for the treatment of GNE myopathy, and filed an Investigational New Drug (IND) Application with the U.S. Food and Drug Administration (FDA) in 2007 to conduct a Phase I/II clinical trial testing the safety and efficacy of ManNAc in GNE myopathy patients. The FDA issued a hold on this clinical trial, citing the need for additional pre-clinical studies. TRND supported the completion of two pivotal animal toxicology studies and generated required data on the manufacturing processes to produce the final drug product. This work allowed TRND to complete the IND Application filing to gain FDA approval to lift the clinical hold preventing initiation of human trials. To gather the information on the disease required for a clinical trial, TRND scientists began a natural history study of GNE myopathy disease progression in 2011. After clearance from the FDA, a Phase I clinical study was initiated in GNE myopathy patients at the NIH Clinical Center. This study has concluded, and a Phase II clinical trial is now underway.