ABSTRACT
Gene Therapies for Muscular Dystrophies D om inic J . W e lls
Gene therapy for the muscular dystrophies aims to restore the normal biochemistry by either modifying the damaged gene (or mRNA) or by expression of a therapeutic transgene. Animal models, mostly mice, are available for many of the muscular dys trophies and so can be used to test gene therapy strategies. Germ-line gene therapy (transgenic) experiments in mouse models have been valuable in assessing the potential of different thera peutic genes. The majority of gene therapy studies have been conducted in the mdx mouse model of the commonest muscular dystrophy, Duchenne muscular dystrophy. Most somatic gene therapy experiments have studied the effects of local administration but for clinical ben efit it will be essential to develop suitable systems for treating multiple muscles at once. Im mune system responses to the gene vectors and the therapeutic protein are concerns for human clinical trials. Currendy the use of antisense oligonucleotides to modify splicing to produce a translatable mRNA, adeno-associated virus gene transfer and regional vascular delivery of plas mid DNA appear to be the most promising gene therapy approaches to the treatment of mus cular dystrophies.
