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         Cooperative studies on molecular pathogenesis, diagnostic methodology and therapeutics for muscular dystrophy and related disorders

Cooperative studies on molecular pathogenesis, diagnostic methodology and therapeutics for muscular dystrophy and related disorders

  • Principal Investigator: Yoshihide Sunada, MD, PhD
    Department of Neurology, Kawasaki Medical School

Objectives:

Muscular dystrophy is one of the most devastating diseases for which there is no effective therapy at present. Although a considerable number of causative genes for the numerous types of muscular dystrophy have been identified in the last twenty years, the underlying molecular pathogenesis remains to be determined. The aim of this project is to promote translational research to develop novel diagnostic methods and therapeutics on the basis of the underlying molecular pathogenesis of muscular dystrophy. To achieve these objectives, a Research Grant totaling over half a million US$ a year has been provided by the Ministry of Health, Labour and Welfare to the research consortium consisting of 40 researchers from all over Japan, headed by Professor Yoshihide Sunada.

Major Achievements:

  • Identification of MG53 which plays an important role in the process of membrane repair and thus may be involved in the pathogenesis of muscular dystrophy.
  • Demonstration of ER stress in the pathogenesis of caveolinopathy even without the accumulation of mutant caveolin-3 proteins.
  • Demonstration of an essential role of N-glycosylation for the glycosyltransferase activity of both POMT1 and POMT2, which are involved in the pathogenesis of α-dystroglycanopathy.
  • Identification of mesenchymal precursor cells that can differentiate into adipocytes in the perivascular interstitium of skeletal muscle. This finding could provide insights into the origin of fat tissue infiltration during the dystrophic process.
  • Development of a novel therapeutic strategy, comprising protein anchoring therapy, by introducing the collagen Q gene with an AAV viral vector in model mice with endoplate acetylcholinesterase deficiency.
  • The sugar chain modification of α-dystroglycan was restored by Large, a molecule with glycosyltransferase activity for the treatment of FCMD. Thus, Large would be a good target molecule for the treatment of α-dystroglycanopathy.