Current understanding of dystrophin-related muscular dystrophy and therapeutic challenges ahead

Chin Med J (Engl). 2006 Aug 20;119(16):1381-91.

Abstract

Objective: To review the recent research progress in dystrophin-related muscular dystrophy includes X-linked hereditary Duchenne and Becker muscular dystrophies (DMD and BMD).

Data sources: Information included in this article was identified by searches of PUBMED and other online resources using the key terms DMD, dystrophin, mutations, animal models, pathophysiology, gene expression, stem cells, gene therapy, cell therapy, and pharmacological. Study selection Mainly original milestone articles and timely reviews written by major pioneer investigators of the field were selected.

Results: The key issues related to the genetic basis and pathophysiological factors of the diseases were critically addressed. The availabilities and advantages of various animal models for the diseases were described. Major molecular and cellular therapeutic approaches were also discussed, many of which have indeed exhibited some success in pre-clinical studies but at the same time encountered a number of technical hurdles, including the efficient and systemic delivery of a functional gene and myogenic precursor/stem cells to repair genetic defects.

Conclusions: Further understanding of pathophysiological mechanisms at molecular levels and regenerative properties of myogenic precursor/stem cells will promote the development of multiple therapeutic strategies. The combined use of multiple strategies may represent the major challenge as well as the greatest hope for the therapy of these diseases in coming years.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dystrophin / genetics
  • Dystrophin / physiology*
  • Genetic Therapy / methods
  • Humans
  • Models, Biological
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / physiopathology*
  • Muscular Dystrophies / therapy
  • Mutation / genetics
  • Utrophin / therapeutic use

Substances

  • Dystrophin
  • Utrophin