Function Induced Modifications of Gene Expression: an Alternative Approach to Gene Therapy of Duchenne Muscular Dystrophy

Abstract

In Duchenne muscular dystrophy a large gene that codes for dystrophin is altered. The possibility that the defective gene/protein could be at least in part substituted by other molecules that the diseased muscle is able to produce and that have a function similar to that of dystrophin is being discussed. Muscle fibres have a tremendous adaptive potential, and the expression of several protein isoforms can be induced by either stretch or long-term change of activity. The exploitation of this ability of muscle cells to express new genes, which would code for proteins that will not be alien to the individual, for treatment of Duchenne muscular dystrophy is being considered. The argument for this approach is strengthened by results that in patients with Duchenne muscular dystrophy the progress of the disease can be slowed with changes of muscle activity.

Progressive resistance voluntary wheel running in the mdx mouse

“…Indeed, resistance wheel running by non‐diseased mice and rats is effective in eliciting these types of adaptations in both cardiac and skeletal muscles 10–12. Although it has been posited that resistance exercises may exploit adaptive processes in dystrophic muscle to strengthen force‐bearing and ‐transmitting structures,13 whether or not these adaptations actually occur in dystrophic muscle has not been tested.…”

Inducing muscle hypertrophy as a therapeutic strategy for muscular dystrophies. 122nd ENMC International Workshop, Naarden, The Netherlands, 28–30 November 2003

“…Nevertheless a change in muscle phenotype from fast to slow may be beneficial to muscles lacking dystrophin, for the 'tonic' regime of activity strengthens the cytoskeletal elements of the muscle fibre. The functional benefit of inducing transcription and protein changes towards the slow phenotype in dystrophic muscle using electrical stimulation was presented [15].…”