Duchenne muscular dystrophy: promising early-stage clinical trials to watch

ABSTRACT

Introduction

Current therapies are unable to cure Duchenne muscular dystrophy (DMD), a severe and common form of muscular dystrophy, and instead aim to delay disease progression. Several treatments currently in phase I trials could increase the number of therapeutic options available to patients.

Areas covered

This review aims to provide an overview of current treatments undergoing or having recently undergone early-stage trials. Several exon-skipping and gene therapy approaches are currently being investigated at the clinical stage to address an unmet need for DMD treatments. This article also covers Phase I trials from the last 5 years that involve inhibitors, small molecules, a purified synthetic flavanol, a cell-based therapy, and repurposed cardiac or tumor medications.

Expert opinion

With antisense oligonucleotide (AON) treatments making up the majority of conditionally approved DMD therapies, most of the clinical trials occurring within the last 5 years have also evaluated exon-skipping AONs. The approval of Elevidys, a micro-dystrophin therapy, is reflected in a recent trend toward gene transfer therapies in phase I DMD clinical trials, but their safety and efficacy are being established in this phase of development. Other Phase I clinical-stage approaches are diverse, but have a range in efficacy, safety, and endpoint measures.

KEYWORDS:

• Clinical trial
• Duchenne muscular dystrophy (DMD)
• exon-skipping therapy
• gene therapy
• micro-dystrophin
• mini-dystrophin
• phase I
• antisense oligonucleotide

Article highlights

• Small molecule, cell-based, synthetic flavanol, and inhibitor treatments have also been investigated in phase I trials as potential treatment alternatives to corticosteroids.

• Multiple next-generation exon-skipping therapies in ongoing phase I trials possess modifications to improve their potency and delivery.

• Variations in the design and vectors of DMD gene therapy options aim to minimize side effects, but show mixed outcomes.

• Existing drugs are being repurposed to see their effects on addressing the inflammatory responses or the cardiomyopathy caused by DMD

Declaration of interests

T Yokota is a founder and shareholder of OligomicsTx, which aims to commercialize antisense oligonucleotide technology. 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.