Introduction

Individually, all myopathies are classified as rare disorders by the NIH Office of Rare Diseases, and Orphanet, which respectively define rare diseases as those affecting less than 200,000 people in the US and 1 in 2,000 Europeans (INSERM and French Ministry of Health 2008; National Institutes of Health Office of Rare Diseases Research 2009). Among all muscular dystrophies, X-linked recessive Duchenne muscular dystrophy (DMD) is the most common (1/3,500 newborn males; Flanigan et al. 2001), followed by the dominant disorders, myotonic dystrophy type 1 (DM1; 1/8,000; Harper 1989) and facioscapulohumeral muscular dystrophy (FSHD; 1/15,000-20,000; Flanigan et al. 2001; Tawil and Van Der Maarel 2006). However, a recent Orphanet report of disease prevalence in Europe places FSHD first, followed by DMD

Department of Pediatrics and Center for Gene Therapy, The Ohio State University, Columbus, OH, 43205, USA

e-mail: [email protected]

DOI 10.1007/978-1-4419-1207-7_7, © Springer Science+Business Media, LLC 2010

and DM (Table 7.1; INSERM and French Ministry of Health 2008). Mutations in at least 29 known genes cause various dominant muscular dystrophies and other related myopathies, and there are at least seven other clinically characterized disorders that have yet to be linked to specific genes (Table 7.1). Collectively, these dominant myopathies approach a prevalence that classifies them as common disorders (~1/2,400 to ~1/3,200'). This is significant as similar gene silencing strategies, with modifications depending on genetic etiology, may be effective for treating most dominant myopathies. Thus, proof-of-principle demonstration of RNA interference (RNAi) therapeutic efficacy in one myopathy could broadly impact an entire class of disorders.

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