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’.