第50回日本神経学会総会
＜シンポジウム5―1＞難治性筋疾患の病態機序―CK発見から50年―治療の時代へ縁取り空胞をともなう遠位型ミオパチーの治療法開発
西野 一三, May Christine V. Malicdan, 野口 悟
国立精神・神経センター神経研究所疾病研究第一部〔〒187-8502 東京都小平市小川東町4-1-1〕
Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion body myopathy, is an autosomal recessive disorder caused by homozygous or compound heterozygous missense mutations in GNE which encodes a protein with two enzymatic activities in sialic acid biosynthesis: UDP-GlcNAc 2-epimerase and ManNAc kinase. The disease starts from 15-40 years and is slowly progressive. DMRV preferentially affects tibialis anterior and hamstrings muscles, and has characteristic findings in muscle pathology which include rimmed vacuoles, tubulofilamentous inclusions, deposition of amyloid, and phosphorylated tau. We generated DMRV mice (Gne-/-hGNE D176V-Tg) by crossmating Gne knock-out heterozygous mouse and human GNE p.D176V transgenic mouse. This model mouse recapitulates DMRV clinically, pathologically, and biochemically by developing muscle weakness and atrophy from 21 weeks, amyloid deposition from 31 weeks, and rimmed vacuoles and phosphorylated tau from 41 weeks while having lifelong hyposialylation. We gave three types of GNE metabolites, ManNAc, NeuAc and sialyllactose, to DMRV mice orally from 15 weeks until 55 weeks of age. Sialic acid supplementation almost completely precluded the disease and virtually no sign of DMRV was seen even at 55 weeks of age, indicating that decreased sialic acid is the cause of myopathic phenotype and sialic acid supplementation can prevent the disease process.
Full Text of this Article in Japanese PDF (415K)
(臨床神経, 49：852−855, 2009)
key words：遠位型ミオパチー, 遺伝性封入体ミオパチー, 縁取り空胞, シアル酸, GNE
（受付日：2009年5月21日）
