Novel therapies for muscular dystrophy and other muscle wasting conditions

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Abstract
The muscular dystrophies are generally characterised by progressive skeletal muscle wasting and weakness. Duchenne muscular dystrophy (DMD), an X-linked disorder, is the most severe of all the dystrophies and is caused by a variety of mutations and deletions in the dystrophin gene. In the absence of dystrophin expression, the skeletal muscles of boys with DMD undergo continuous cycles of degeneration and regeneration of muscle fibres that lead to a progressive wasting of the skeletal muscles. At age 10 years, DMD patients have only 25% of the muscle mass of healthy children and the functional burden on their weakened muscles is too great for normal ambulation well before this time. They become dependent on a wheelchair before their early teens and die of respiratory or heart failure by their early 20’s. There is a profound need for therapeutic intervention strategies that aim to cure or ameliorate the dystrophic condition and improve the quality of life for these patients. Therapeutic approaches for muscular dystrophy fall into two classes: those that attempt to ameliorate the dystrophic condition through pharmacological interventions, or those that attempt to overcome the gene defect. The greatest likelihood of a cure for DMD and other muscular dystrophies will eventually be derived from gene therapy. However, problems continue to plague this research, including: the limitation of the spread of expression from injection sites in the muscle, the longevity of expression, the need for systemic delivery, vector design and carrying capacity, and difficulties with immunosuppression. Sadly, until these techniques are perfected, boys with DMD will die and patients with other less severe neuromuscular conditions will continue to lose muscle mass and function. This review examines recent (1997 - 2000) patents on novel therapies for muscular dystrophy and evaluates their potential for ameliorating muscle wasting and/or improving muscle function.