Perspectives on the advances in the pharmacotherapeutic management of Duchenne muscular dystrophy

ABSTRACT

Introduction

Duchenne muscular dystrophy (DMD) is a progressive genetic disease characterized by muscular weakness with a global prevalence of 7.1 cases per 100,000 males. DMD is caused by mutations of the dystrophin gene on the X chromosome, which is responsible for dystrophin protein production. Dystrophin is a cytoskeletal protein that contributes to structural support in muscle cells. DMD mutations result in dystrophin protein deficiency, which leads to muscle damage and the associated clinical presentation.

Areas covered

Corticosteroids such as prednisone and deflazacort are routinely given to patients to treat inflammation, but their use is limited by the occurrence of side effects and a lack of standardized prescribing. Exon-skipping medications are emerging as treatment options for a small portion of DMD patients, even though efficacy is uncertain. Many new therapeutics are under development that target inflammation, fibrosis, and dystrophin replacement.

Expert opinion

Because of side effects associated with corticosteroid use, there is need for better alternatives to the standard of care. Excessive cost is a barrier to patients receiving medications that have yet to have established efficacy. Additional therapies have the potential to help patients with DMD, although most are several years away from approval for patient use.

KEYWORDS:

• CAP-1002
• corticosteroids
• exon-skipping
• gene therapy
• givinostat
• idebenone
• ifetroban
• TAS-205
• tamoxifen
• vamorolone

Article highlights

• Duchenne muscular dystrophy is an X-linked recessive trait caused by deletions and duplications (70%–80%) and point mutations (20%–30%).

• DMD presents around 3 years of age with difficulty walking, which progresses to loss of ambulation, scoliosis, need for ventilatory support, and cardiomyopathy.

• Corticosteroid therapy is the accepted standard of care in DMD, despite unfavorable side effects.

• Four exon-skipping therapies have reached FDA approval since 2016 with limited clinical efficacy.

• Additional agents with a variety of mechanisms are being developed to improve symptoms, quality of life, and lengthen life span.

Declaration of interest

The authors have no 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.