Charcot-Marie-Tooth disease: a review of clinical developments and its management - What's new in 2025?

Abstract

Introduction: Charcot-Marie-Tooth disease (CMT) understanding and diagnostic rates are improving. Symptomatic management is still the only option, but many therapeutic approaches are under investigation, some in the clinical trial phase.

Areas covered: Through a comprehensive search in PubMed, the ClinicalTrials.gov website, and the latest abstracts on the topic, the authors review the diagnostic advances and promising treatments, focusing on pharmacological and gene therapy/silencing approaches, and on clinical trial challenges. They also review current CMT management, including rehabilitation, orthotics, and associated symptoms and comorbidities.

Expert opinion: The CMT field is evolving rapidly, with significant advances in genetic diagnosis and disease recognition. International networks and patient organization partnerships are vital for progress, enabling collaboration and large-scale studies. Metabolic neuropathies are relatively easier to target, and interim analysis results from the CMT-SORD trial suggest govorestat may become the first approved CMT drug. Gene therapy shows promise but currently faces safety and targeting challenges; PMP22 silencers for CMT1A are close to being tested in patients. New drugs, such as HDAC6 inhibitors, are also approaching the clinical trial phase, despite existing hurdles. Supportive care, including rehabilitation and orthotics, continues to improve quality of life. There is optimism that within the next decade, approved therapies will reduce disease burden.

Keywords: Charcot-Marie-Tooth (CMT); clinical trials; gene therapy; long read sequencing; novel treatments; sorbitol dehydrogenase; surrogate biomarkers; symptomatic management.