Therapeutic potential of orphan drugs for the rare skeletal muscle diseases

Abstract

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.

Keywords:

• muscle disease
• muscle wasting
• muscular dystrophy
• skeletal muscle

Declaration of interest

Prof G Lynch is a scientific consultant and shareholder in N-Gene Research Laboratories (NY, U.S.A.) and an editorial board member of Expert Opinion on Emerging Drugs. The Basic and Clinical Myology Laboratory is grateful for project grant support from the Australian Research Council, National Health and Medical Research Council, Muscular Dystrophy Association (U.S.A.) and the Association Francaise contre les Myopathies (France). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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