Innovations in Gene Therapies for Neuromuscular Disorders and Peripheral Neuropathies

Neuromuscular and peripheral nerve diseases represent a diverse group of debilitating conditions that compromise motor and sensory function, often leading to progressive disability and reduced quality of life. In recent years, gene therapy has emerged as one of the most transformative approaches for inherited neuromuscular disorders, providing targeted intervention by replacing or correcting defective genes. Adeno-associated viral (AAV) vectors marked a major step forward in precision medicine. Recent clinical approvals and ongoing trials have demonstrated that gene replacement and editing strategies can achieve meaningful functional benefits in spinal muscular atrophy and Duchenne muscular dystrophy. At the same time, applications of gene-based delivery systems for acquired neuropathies—such as immune-mediated diseases or amyotrophic lateral sclerosis—are rapidly expanding, leveraging advances in vector design and precision targeting to modulate immune or inflammatory pathways and promote neuroprotection. Despite this progress, fundamental challenges remain. High systemic vector doses, immunogenicity, off-target effects, toxicity, and transgene size limitations continue to hinder broader translation, underlining an urgent need for deeper mechanistic understanding and next-generation delivery solutions.

This Research Topic aims to consolidate multidisciplinary research efforts focused on improving the efficacy, safety, and translational potential of gene therapies for both inherited and acquired neuromuscular disorders and peripheral neuropathies. It seeks to explore innovative strategies in vector optimization, immune evasion, and transgene engineering, as well as to foster collaboration between fundamental and clinical research communities. The goal is to identify novel therapeutic platforms and establish a framework for overcoming existing technical and biological barriers, ultimately accelerating the translation of bench discoveries into viable clinical interventions and real-world patient benefit.

To gather further insights underpinning the successful implementation of gene therapies for neuromuscular and peripheral neuropathies, we welcome submissions across a diverse range of manuscript types supported by the journal—including Original Research, Brief Research Reports, Perspectives, Protocols, Mini-Reviews, and more—exploring, but not limited to, the following themes:
- Advances in viral vector-based gene therapies for inherited neuromuscular and peripheral nerve diseases
- Gene therapy as a delivery platform for neuroprotective or immunomodulatory agents in acquired conditions
- AAV capsid engineering strategies and novel vectors for enhanced neuromuscular tropism and safety
- Immunological responses, toxicity mechanisms, and mitigation approaches in AAV-based gene therapy
- Gene editing and base editing innovations for precise genomic correction
- Non-viral modalities, including antisense oligonucleotides and RNA-based therapies
- Exon skipping strategies in neuromuscular disorders (e.g., Duchenne muscular dystrophy)
- Animal models, iPSC-derived systems, and organoid platforms for efficacy and safety evaluation
- Regulatory, ethical, and clinical frameworks accelerating the transition from experimental therapies to approved treatments
- Financial and ethical implications of developing and accessing gene therapies for neuromuscular disorders

Articles will be published online as soon as they are accepted after peer review and approved for publication.

Topic Editor Maria Grazia Biferi was employed by Spark Therapeutics, a Roche company, and holds equity in the company. Topic Editor Helena Costa Verdera was employed by the same company, Spark Therapeutics. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review

Keywords: gene therapy, AAV vectors, neuromuscular disorders, peripheral neuropathy, muscular dystrophy, spinal muscular atrophy, gene editing, capsid engineering, antisense oligonucleotides

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.