CMT Orgs Come together to Advocate for New Clinical Trial Framework

Organizations focused on Charcot-Marie-Tooth (CMT) disease have aligned with clinicians, and pharmaceutical companies to share a set of recommendations for how CMT clinical trials should be designed, with the recommendations published in Journal of the Peripheral Nervous System on August 4, 2026.

The publication comes from organizations including CMT4B3 Research Foundation, Charcot-Marie-Tooth Association (CMTA), CMT Research Foundation (CMTRF), Hereditary Neuropathy Foundation (HNF), and the Muscular Dystrophy Association (MDA), withadditional input from clinicians and pharmaceutical companies.

The first of its kind, these recommendations give drug developers a clearer, more consistent framework as they design trials and bring treatments to the FDA for review. This framework is especially important because CMT has many subtypes with unique clinical presentations, complicating both clinical trial design and regulatory review. 

There are no currently approved treatments for Charcot-Marie-Tooth disease.

The paper is the product of “ToPIC: CMT” (Together Patients, Industry and Clinicians), a group dedicated to providing a unified voice to help steer and de-risk clinical development for promising CMT therapeutics. The publication reflects years of collaborative work across the field and is available in open access courtesy of the CMT Research Foundation.

Top Takeaways and Recommendations

• Flexible trial designs to limit placebo exposure. Because CMT is rare and progressive, the guidance supports approaches like single-participant designs and externally controlled trials, so fewer patients need to be exposed to placebo to generate persuasive evidence.

• Enrollment based on clinical phenotype (physical presentation), not just genetic subtype. Many CMT subtypes share similar disease courses. The guidance recommends trial populations reflect shared clinical presentation rather than narrowly restricting enrollment by genetic mutation, when appropriate, which can speed enrollment and make results more broadly applicable.

• Disease-specific, function-based endpoints. A central goal of this effort was defining how efficacy is measured. The guidance calls for endpoints that capture change across a wide range of disease severity, and highlights validated performance-based outcome assessments and patient-reported outcomes, such as the CMT Health Index, as strong options.

• A defined role for biomarkers. Biomarkers such as neurofilament light chain, PMP22 expression, and MRI-based muscle fat fraction calculations are identified as tools that can support dose selection, prognosis, and in some cases serve as surrogate endpoints for accelerated approval.

• Support for early and lifelong treatment strategies. Given that early intervention may preserve function before irreversible damage occurs, the guidance encourages enrolling younger patients when scientifically and ethically justified, while also emphasizing the need to study safety and efficacy across the full lifespan of the disease.

• Practical safety and labeling frameworks. Recommendations cover appropriately sized pediatric safety databases, considerations specific to gene therapy products, and a path for extrapolating benefit across CMT subtypes when scientifically justified, rather than requiring separate trials for every genetic variant.

Together, these recommendations are meant to give trial sponsors a consistent, predictable framework to design around, so they can "begin with the end in mind" with a clearer path toward approval.

A Field-Wide Effort

This paper would not have been possible without the CMT organizations, clinicians, and pharmaceutical partners who came together to shape it. We want to acknowledge everyone who contributed, along with the clinical partners whose research and scales underpin much of the guidance. The full list of contributors and their roles is below.

The Partners Behind ToPIC: CMT

Coordination

• Dr. Shannon Strom, Senior Vice President of Regulatory Affairs, Aerogen Pharma

CMT Organizations

• CMT4B3 Research Foundation: Iris Schultz,Founder and President

• Charcot-Marie-Tooth Association (CMTA): Dr. Suzanne (Sue) Bruhn, CEO, and Dr. Katherine Forsey, Chief Research Officer

• CMT Research Foundation (CMTRF): Susan Ruediger, co-Founder and Chief Mission Officer 

• Hereditary Neuropathy Foundation (HNF): Allison Moore, Founder and CEO 

• Muscular Dystrophy Association (MDA): Dr. Brian Lin, Director of Research  

Additional Steering Guidance

• Jenneen DiFiore (Thermo Fisher Scientific), Dr. Susie McCune (Thermo Fisher Scientific)

Clinicians

• Dr. Charles Abrams (University of Illinois Chicago), Dr. Joshua Burns (University of Sydney), Dr. Vera Fridman (University of Colorado), Dr. David Herrmann (University of Rochester), and Dr. Mike Shy (University of Iowa) contributed clinical expertise, including work behind many of the CMT-specific functional and quality of life scales referenced in the guidance.

Pharmaceutical Companies

• Novartis, NMD Pharma, Armatus Bio, Applied Therapeutics, Thermo Fisher Scientific, Actio Biosciences, Alesta Therapeutics, and Elpida Therapeutics provided operational perspective on building functional scales and efficacy endpoints into clinical programs.