Efficacy of Aceneuramic Acid for Distal Myopathy with Rimmed Vacuoles

Abstract

Distal myopathy with rimmed vacuoles (DMRV), also known as GNE myopathy, is a rare disease affecting the distal muscles, such as the tibialis anterior muscle. The GNE gene, which codes for a key enzyme in the sialic acid biosynthesis pathway, is mutated in a homozygous or compound heterozygous manner, and the lack of sialic acid in skeletal muscle is the critical underlying mechanism in DMRV pathogenesis. DMRV mouse models were established, and supplementation with sialic acid improved the phenotypes of the models. A phase 1 clinical trial using aceneuramic acid was conducted at Tohoku University Hospital, Japan, followed by trials using a slow-release product. A phase II/III study, subsequent extended trial, and confirmatory trial were also conducted. Regulatory approval is currently under review.