New and emerging pharmacotherapy for duchenne muscular dystrophy: a focus on synthetic therapeutics

ABSTRACT

Introduction

Duchenne muscular dystrophy (DMD) is the result of X-chromosome-linked mutations to the dystrophin protein gene that prevent the normal development and repair of muscles leading to muscle deterioration. The condition affects nearly 1 in 3,500 males worldwide. Current therapeutics have not been sufficient in providing a cure or resulting in a significant extension in life expectancy, but many therapeutic options are currently under investigation.

Areas covered

This article provides an overview of the current and emerging therapies for DMD giving particular focus to synthetic therapeutic options. The authors further provide their expert opinion.

Expert opinion

Many discrepancies in primary outcomes of trials have led to questions of efficacy for medications, as well as difficulty in securing FDA approval. A standardization of primary outcome strategies, as well as better access to investigational medications, may alleviate some of the controversy and pressures that exist on medication approvals. Many trials have identified cohorts who responded more favorably to medications, despite a lack of significance in the overall intent-to-treat populations. This indicates that more medication screening and personalized treatment with patient-specific targeting might deliver more clinically significant results.

KEYWORDS:

• Corticosteroids
• dystrophin
• eteplirsen
• exon-skipping
• gene therapy
• read-through
• utrophin

Article highlights

• Duchenne muscular dystrophy is a fatal, genetic disorder affecting 1 in 3,500 males.

• Current standard of care utilizes prednisone or deflazacort to control inflammation.

• Read-through therapy, exon-skipping therapy, dystrophin alternatives, and dystrophin replacement are all avenues of research.

• FDA approval of eteplirsen has led to controversy in the outcomes that determine efficacy.

• Improved access to investigational medications and accepted measures of efficacy may alleviate burden surrounding medication approval.

• Additional screening and matching of patient characteristics to those of trial cohorts showing efficacy may help with targeted therapy and improve results.

This box summarizes key points contained in the article.

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 manuscript has not been funded.