Director: Shin'ichi Takeda, MD & PhD

Members of Department of Molecular Therapy are trying to develop fundamental therapy for inherited neuromuscular diseases, especially for Duchenne muscular dystrophy (DMD). DMD is an X-linked muscle wasting disease caused by the absence of dystrophin from the sarcolemma and affects about 1/3500 newborn males.

We have been engaged in three therapeutic approaches to the disease.

The first approach is to deliver the dystrophin gene into dystrophin-deficient muscles by using an adeno-associated virus (AAV) vector (gene therapy). We constructed an AAV vector encoding micro-dystrophin, and successfully improved dystrophic phenotypes in dystrophin- deficient mdx mice. To further establish gene therapy for DMD, a new facility for muscular dystrophy dogs was established on March 2001.

The second approach is stem cell-based cell therapy. Adult muscle and bone marrow contain multipotent stem cells, which might be useful to treat muscular dystrophy, and they can be systemically delivered into skeletal muscle via the vascular system.

The third approach is newly designed drug therapy. Up-regulation of utrophin, an autosomal homologue of dystrophin, could be an alternative strategy to treat DMD patients, since up-regulation of endogenous utrophin ameliorates dystrophic phenotypes. We are now screening drugs which activate utrophin expression, and also studying the transcriptional and translational regulation of the utrophin gene.

Besides research on therapy for DMD, we are studying the functions of dystrophin-associated proteins (sarcoglycans, syntrophins, nNOS, Aquaporin-4) and other relevant molecules, such as dysferlin to clarify molecular mechanisms of other types of muscular dystrophy.