[Sialic Acid supplementation therapy for distal myopathy with rimmed vacuoles].

Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion body myopathy, is an autosomal recessive disease that typically affects tibialis anterior and hamstring muscles in young adults although other muscles are also involved in later stages. The disease is caused mostly by missense mutations in the GNE gene that encodes a protein with two enzymatic activities in sialic acid biosynthetic pathway: UDP-GlcNAc 2-epimerase and ManNAc kinase, respectively catalyzing the rate-limiting step and the subsequent reaction. Accordingly, sialic acid production is reduced in patients' cells and cells are hyposialylated. We have previously shown that this hyposialylation status can be recovered by simply giving sialic acid, suggesting that hyposilylation status in the muscle should be the cause of myopathy. In support of this notion, myopathic manifestations were virtually completely suppressed by oral administration of sialic acid in our DMRV model mice. Similar efficacy was seen also by ManNAc, precursor of sialic acid, or sialyllactose, a conjugate form of sialic acid. Based upon these in vitro and in vivo results, phase I clinical trial for sialic acid supplementation therapy for human patients was conducted in Japan in 2011. Another phase I trial, using slow release tablets of sialic acid, is currently in progress in the US. Hopefully, phase II trial to see the efficacy of the therapy will be initiated soon.