DERMAL FIBROBLASTS CONVERT TO A MYOGENIC LINEAGE IN MDX MOUSE MUSCLE

Duchenne muscular dystrophy is a primary muscle disease that manifests itself in young boys as a result of a defect in a gene located on the X-chromosome. This gene codes for dystrophin, a normal muscle protein that is located beneath the sarcolemma of muscle fibres, Therapies to alleviate this disease have centred on implanting normal muscle precu rsor cells into dystrophic fibres to compensate for the lack of this g ene and its product. To date, donor cells for implantation in such the rapy have been of myogenic origin, derived from paternal biopsies. Suc cess in human muscle, however, has been limited and may reflect immune rejection problems. To overcome this problem the patient's own myogen ic cells, with the dystrophin gene inserted, could be used, but this c ould lead to other problems, since these cells are those that are func tionally compromised by the disease. Here, we report the presence of h igh numbers of dystrophin-positive fibres after implanting dermal fibr oblasts from normal mice into the muscle of the mdx mouse - the geneti c homologue of Duchenne muscular dystrophy. Dystrophin-positive fibres were also abundant in mdx muscle following the implantation of cloned dermal fibroblasts from the normal mouse. Our results suggest the in vivo conversion of these non-myogenic cells to the myogenic pathway re sulting in the formation of dystrophin-positive muscle fibres in the d eficient host. The use of dermal fibroblasts may provide an alternativ e approach to the previously attempted myoblast transfer therapy, whic h in human trials has yielded disappointing results.