Therapeutic potential of orphan drugs for the rare skeletal muscle diseases

Introduction: Rare diseases affect ∼350 million people worldwide yet 95% of these diseases do not have a single FDA-approved drug for treatment. The rare skeletal muscle diseases include numerous severe muscle wasting disorders, including spinal muscular atrophy, inclusion body myopathies, glycogen storage disorders and the many muscular dystrophies. While the underlying genetic defects responsible for each of these disorders is usually unique and not always confined to skeletal muscle, muscle fiber atrophy and weakness are common to all of them.Areas covered: Progress in the development of therapies with ‘orphan drug’ status is detailed for some of the rare skeletal muscle diseases. These therapies include drugs at varying stages and progression through the development pipeline such as membrane sealants, anti-inflammatory medications, enzyme replacers, growth promoting agents, anti-fibrotics, as well as gene- and cell-based approaches.Expert opinion: Multiple drugs have received orphan designation for rare muscle diseases and several have entered clinical trials and progressed through the development pipeline. Many drugs enter trials without having undergone sufficiently rigorous preclinical testing in relation to their effects on skeletal muscle structure–function; a shortcoming that could compromise their efficacy for treating the rare muscle diseases. More rigorous preclinical physiological assessments are important for identifying which drugs should advance to clinical trials.