縁取り空胞を伴う遠位型ミオパチーを対象としたアセノイラミン酸の有効性

Efficacy of Aceneuramic Acid for Distal Myopathy with Rimmed Vacuoles

縁取り空胞を伴う遠位型ミオパチーは，10代後半から発症し緩徐に進行する有効な治療法のない難病である。原因遺伝子GNEがシアル酸代謝に関わり，非臨床試験でシアル酸の有効性が示され，東北大学病院はアセノイラミン酸による医師主導第Ⅰ相試験を実施した。その後，海外第Ⅲ相試験と同様のプロトコールにてアセノイラミン酸徐放錠の有効性と安全性を検証する第Ⅱ/Ⅲ相試験を国内5施設で行い，さらにその確認試験も実施した。

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.