A team from the University of Iowa has investigated the effectiveness of gene therapy in advanced stages of muscular dystrophy. The researchers injected an AAV2/9 CMV Large 1 into 14 mice, averaging 38 weeks of age, which are models of congenital muscular dystrophy 1D (CMD 1D) linked to the LARGE 1 gene.
Treated mice show improvements in the dystrophic phenotype that are maintained until the end of the animal’s life:
- restoration of the expression of the functional form of alpha-dystroglycan in the muscle fibres;
- an increase in forepaw grip strength and greater tetanic strength
- restoration of the ability to stand up on the hind legs;
- a halt in the progression of fibrous tissue deposition in the muscle;
- a 40% increase in lifespan: 93% of treated mice live beyond 65 weeks while 50% of untreated mice survive up to 45 weeks;
- an increase in the size of the muscle fibres of the diaphragm and in the capacity to inspire;
- a normalisation of 10 of the 21 previously abnormal metabolites in the plasma metabolome.
