Chapter 11: Drug Discovery Approaches for Rare Neuromuscular Diseases Check Access

Rare neuromuscular diseases encompass many diverse and debilitating musculoskeletal disorders, ranging from ultra-orphan conditions that affect only a few families, to the so-called ‘common’ orphan diseases like Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), which affect several thousand individuals worldwide. Increasingly, pharmaceutical and biotechnology companies, in an effort to improve productivity and rebuild dwindling pipelines, are shifting their business models away from the formerly popular ‘blockbuster’ strategy, with rare diseases being an area of increased focus in recent years. As a consequence of this paradigm shift, coupled with high-profile campaigns by not-for-profit organisations and patient advocacy groups, rare neuromuscular diseases are attracting considerable attention as new therapeutic areas for improved drug therapy. Much pioneering work has taken place to elucidate the underlying pathological mechanisms of many rare neuromuscular diseases. This, in conjunction with the availability of new screening technologies, has inspired the development of several truly innovative therapeutic strategies aimed at correcting the underlying pathology. A survey of medicinal chemistry approaches and the resulting clinical progress for new therapeutic agents targeting this devastating class of degenerative diseases is presented, using DMD and SMA as examples. Complementary strategies using small-molecule drugs and biological agents are included.