Inducing muscle hypertrophy as a therapeutic strategy for muscular dystrophies. 122nd ENMC International Workshop, Naarden, The Netherlands, 28–30 November 2003

Neuromuscular Disorders, 2004

Ketan Patel, Francesco Muntoni - London

Patients with a variety of neuromuscular disorders and most noticeably with muscular dystrophies experience profound muscle wasting. In muscular dystrophies this is believed to be the result of increased muscle damage and progressive loss of regeneration capacity by the satellite cells. Muscle wasting is also a process that occurs during ageing. Recent studies suggest that the muscle atrophy observed both in aged and dystrophic muscle can be effectively counteracted by strategies aimed at inducing an increase in muscle mass. To this end animal models have been developed such as those conditionally over expressing insulin-like growth factor 1 (IGF-1) in skeletal muscle, which resulted in sustained hypertrophy. This not only preserved the muscle mass in ageing skeletal muscle, but also improved the function of dystrophic muscle in the mdx mouse, the animal model for Duchenne muscular dystrophy. Interference with myostatin function by transgenic approach or using blocking antibodies, has resulted in functional improvement of the dystrophic histological and clinical phenotype in mdx mice. These approaches suggest that interfering with the programme of skeletal muscle regeneration and growth can lead to potential benefit in patients with muscular dystrophies and, potentially, other neuromuscular disorders and possibly the entire ageing population. We recently convened a European Neuromuscular Centre Workshop in which 18 participants from five countries (France, Germany, Italy, UK and USA) working on cellular and molecular aspects discussed the topic of ‘inducing muscle hypertrophy as a therapeutic strategy for muscular dystrophies’.