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- Vol.41 No.12
- CLINICA NEUROL, 41: 1154－1156, 2001
- Vol.41 No.12 contents
The 42nd Annual Meeting of the Japanese Society of Neurology
Symposium IX-1: Therapeutic approaches to the intractable diseases
Development of new therapy on muscular dystrophy
Shin' ichi Takeda, M. D. Ph. D.
Department of Molecular Therapy National Institute of Neuroscience National Center of Neurology and Psychiatry
Duchenne muscular dystrophy (DMD) is an X-linked, lethal disorder caused by a defect in the DMD gene. We have previously reported that micro-dystrophins, which have large deletions in rod repeat domain, successfully localize at the sarcolemma and stabilize dystroglycan-sarcoglycan complex in dystrophin-deficient mdx muscle. However, expression of a 3.7-kb micro-dystrophin cDNA, having only one rod repeat showed no effect on dystrophic phenotype. Further transgenic experiments are carrying to seek a functional but small-sized micro-dystrophin cDNA, which can be accommodated into Adeno-associated virus (AAV) vector. In normal muscle, AAV-LacZ vector expresses stably β -gal for a long period, however, we noticed that immune response is evoked by AAV-LacZ vector in mdx muscle. Therefore, for successful gene therapy, it is required to reduce immune response against AAV-dystrophin vector and therapeutic proteins in mdx mice. We have already reported that utrophin was up-regulated at the sarcolemma of mdx mice, when a β -galactosidase-expressing adenovirus vector, AxCALacZ was injected into the skeletal muscle. Moreover, up-regulated utrophin mitigated dystrophic phenotypes. Up-regulation of utrophin was induced by inflammatory response against adenovirus vector-mediated gene transfer and this up-regulation is one of promising tools for treatment of DMD.
(CLINICA NEUROL, 41: 1154－1156, 2001)
key words: Duchenne muscular dystrophy, gene therapy, cell therapy, micro-dystrophin cDNA, Utrophin
(Received: 13-May-01)
