Novel therapies for muscular dystrophy and other muscle wasting conditions

The muscular dystrophies are generally characterised by progressive skeleta l muscle wasting and weakness. Duchenne muscular dystrophy (DMD), an X-link ed disorder, is the most severe of all the dystrophies and is caused by a v ariety of mutations and deletions in the dystrophin gene. In the absence of dystrophin expression, the skeletal muscles of boys with DMD undergo conti nuous cycles of degeneration and regeneration of muscle fibres that lead to a progressive wasting of the skeletal muscles. At age 10 years, DMD patien ts 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 be fore this time. The): become dependent on a wheelchair before their early t eens 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 th ese patients. Therapeutic approaches for muscular dystrophy fall into two c lasses: those chat attempt to ameliorate the dystrophic condition through p harmacological interventions, or those that attempt to overcome the gene de fect. The greatest likelihood of a cure for DMD and other muscular dystroph ies will eventually be derived from gene therapy. However, problems continu e to plague this research, including: the limitation of the spread of expre ssion from injection sites in the muscle, the longevity of expression, the need for systemic delivery, vector design and carrying capacity, and diffic ulties with immunosuppression. Sadly, until these techniques are perfected, boys with DMD will die and patients with other less severe neuromuscular c onditions will continue to lose muscle mass and function. This review exami nes recent (1997 - 2000) patents on novel therapies for muscular dystrophy and evaluates their potential for ameliorating muscle wasting and/or improv ing muscle function.