American researchers have sought to combine two therapeutic approaches in mouse models of FKRP-related limb-girdle muscular dystrophy type R9 (LGMD R9): oral supplementation with 5% ribitol at five weeks of age, followed four weeks later by administration of a dose of 1e13 vg/kg (low) or 5e13 vg/kg (high) of gene therapy (AAV9-FKRP). Compared with mice treated with ribitol alone or gene therapy alone, the doubly-treated mice showed :
- a greater or equal median life expectancy (at least 104 weeks) ;
- an intensification of the alpha-dystroglycan glycosylation signal in the heart, limb muscles and diaphragm;
- a 10% reduction in muscle fibrosis ;
- a more even distribution of muscle fibre size;
- a greater or equal reduction in the number of fibres with central nuclei.
The investigators hypothesised that ribitol would stabilise the progression of the disease before the start of gene therapy and would help to maintain and prolong the efficacy of the latter. This study demonstrates the potential of a dual therapeutic approach providing both a functional gene and the substrate for its protein.
