Combinatorial gene therapy strategies for treating muscular dystrophies

Abstract

Muscular dystrophies are commonly associated with progressive loss of muscle mass and strength as a consequence of ongoing myofibril degeneration and wasting. Genetic therapies have been proposed as interventions for disorders where specific monogenic mutations have been linked to the origin of disease. For muscular dystrophies of this nature, a single-gene therapy intended to introduce a surrogate gene in lieu of the defective endogenous copy (or to ablate a dominant negative state) may prove sufficient to prevent or reverse the development of disease. However, the increasingly severe morphological disruption and depletion of functional muscle fibers observed with disease progression may pr..