DEX-M74 for GNE Myopathy

DEX-M74 治疗 GNE 肌病

• 批准号: 9205573
• 负责人: Na Yang
• 金额: $ 200.38万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9205573
• 关键词: DEX; M74; GNE; Myopathy

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.

GNE肌病是一种罕见的成人发病肌肉疾病，其特征是进行性肌肉无力，在发病后10至20年内导致严重的丧失行为能力。GNE肌病是一种遗传性疾病，可追溯到GNE基因突变。GNE编码一种酶，催化唾液酸（SA）生物合成的前两个步骤。据推测，随后SA产生的不足会导致肌糖蛋白唾液化减少，从而导致肌肉变性。