A preclinical trial of sialic acid metabolites on distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy, a sugar-deficient myopathy: a review

摘要

Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion body myopathy (hIBM), is a moderately progressive hereditary muscle disorder affecting young adults. DMRV/hIBM is characterized clinically by muscle atrophy and weakness initially involving the distal muscles, and pathologically by the presence of small angular fibers, formation of rimmed vacuoles and deposition of various proteins in the muscle fibers. This disease is known to be caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene, which encodes the essential enzyme in sialic acid biosynthesis, leading to a reduction of sialic acid levels in the serum and skeletal muscles of affected patients. As it is a metabolic disease, metabolite supplementation is theoretically one of the therapeutic options. In this review, recent animal models for DMRV/hIBM are briefly characterized followed by a focus on the administration of sialic acid metabolites as a reliable therapeutic option to DMRV/hIBM with the following points highlighted: the property of compounds, the pharmacokinetic metabolism in vivo, and the therapeutic effects on the DMRV/hIBM mouse model.