New treatments in spinal muscular atrophy: an overview of currently available data

ABSTRACT

Introduction: Spinal muscular atrophy (SMA) is one of the most common inherited neuromuscular disorders. It causes progressive muscle weakness and results in significant disability. Until recently, there were no drugs available for the treatment of SMA. Several phase 1–3 studies, including three double-blind randomized placebo-controlled studies have demonstrated the efficacy of disease-modifying approaches including gene replacement therapy, antisense oligonucleotides, and splicing modifiers.

Areas covered: This article covers the publically available data on therapeutic strategies that address the underlying cause of SMA and clinical data available on approved treatments and drugs in the pipeline.

Expert opinion: The newer therapeutic options in SMA have a good safety profile and deliver a therapeutic benefit in most patients. It is essential that the recommended standards of care are delivered along with the drugs for the best outcomes. No biomarkers to distinguish responders from non-responders are available; it is important that biomarkers be identified. Early treatment is essential for the maximum efficacy of the newly available treatments.

KEYWORDS:

• Spinal muscular atrophy
• antisense oligonucleotide
• splicing modifiers
• gene therapy
• nusinersen
• risdiplam
• branaplam

Article highlights

• Spinal muscular atrophy (SMA) is one of the most common inherited neuromuscular disorders.

• Innovative therapies of SMA target SMN gene, SMN2 gene splicing, and muscle proliferation or contraction

• Several phase 1-3 studies, including three double-blind randomized placebo-controlled studies have demonstrated the efficacy of diseases modifying approaches including gene replacement therapy, antisense oligonucleotide, and splicing modifiers.

• Earlier treatment is associated with better efficacy, which has prompted newborn screening programs.

• Questions remain open on the relative efficacy of the different approaches and the potential interest of combining them simultaneously or sequentially.

This box summarizes the key points contained in the article.

Declaration of interest

L Servais is a member of the board and/or has consulted for Avexis, Roche, Biogen Idec, and Cytokinetics. He is also the principal investigator for trials funded by Biogen Idec, Avexis, and Roche. 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 manuscript was not funded.