Muscular dystrophy is defined as "a group of hereditary disorders with the major symptom of progressive
muscle weakness due to muscle fiber degeneration and
necrosis". After the discovery of the
dystrophin gene and the gene product for
Duchenne muscular dystrophy in 1986, there has been remarkable progress in the differential diagnosis and in understanding the pathogenetic mechanism of muscle fiber
necrosis. With discoveries of genes responsible for many other disorders, the classification of
muscular dystrophy has become more complicated; for instance, there are at least 15 diseases in the
limb-girdle muscular dystrophy (LGMD) group, including the autosomal dominant forms, LGMD1A-1E and the recessive forms, LGMD2A-2I. Among them, gene defects in the
sarcoglycan complex (
sarcoglycanopathy) have been added to LGMD2C-2F.
Sarcoglycanopathy seems to be rare in Japan since only 6-7% of LGMD patients had this defect. There are two major possible strategies in treating these patients. One is gene therapy, which is recently being investigated in the mdx mouse by using adenovirus-associated virus (AAV) vector inserted with a microdystrophin gene. Dr Takeda has reported favorable results in mdx mouse muscle with this method. Another is regeneration
therapy using stem cells. There are many barriers to overcome to treat patients with stem cells isolated from bone marrow. The most difficult problem to solve is how to culture the stem cells to increase their numbers for application and how to introduce the normal
dystrophin gene into these cells.