Immunobiology and the future of myoblast transfer therapy

Myoblast transfer therapy (MTT) is a cell-mediated gene transfer method aim ed at the restoration of normal dystrophin expression in Duchenne muscular dystrophy (DMD). Initial clinical MTT trials were conducted amid much contr oversy, as they were based on very few animal studies. Unfortunately, the t rials were of little therapeutic benefit. As a result, there has been a ren aissance of interest in experimental studies in animal models. In MTT, myob lasts are obtained by muscle biopsy from normal, i.e., dystrophin-positive, donors, expanded in culture, and injected directly into the muscles of dys trophic recipients. The major requirement for successful MTT is the surviva l of injected donor myoblasts in the host environment. However, a vast majo rity of donor cells fail to survive for more than 1 h after injection, and very few last beyond the first week. This review on the immunological aspec ts of MIT focuses in particular on the roles of specific components of the host immune response, the effects of tissue culture on donor cells, and str ategies under development to circumvent the problem of donor myoblast death after injection in vivo.