{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:04:14Z","timestamp":1790071454769,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Charcot\u2013Marie\u2013Tooth disease (CMT) encompasses a heterogeneous group of inherited peripheral neuropathies. Despite being the most common genetic neurological condition, individual CMT subtypes are rare, presenting unique challenges for therapeutic development. The Together Patients Industry Clinicians versus CMT (ToPIC: CMT) Advocacy Group was formed with a diverse group of patient advocacy groups, clinician\u2010scientists who treat patients with CMT, and pharmaceutical industry representatives to develop a common guidance on development of new treatments for CMT with clear expectations for meaningful patient outcomes and objective assessments of improvement. The ToPIC: CMT Group developed recommendations for clinical development of drugs and biological products for treating CMT, addressing trial design considerations for this rare progressive disease. Key challenges in CMT include small patient populations, variable disease progression, and the need for sensitive outcome measures. Recommendations emphasize flexible trial designs including adaptive designs, external controls, and single\u2010participant designs when scientifically justified. Where possible, broad inclusion criteria based on clinical phenotype rather than genetic subtype alone are recommended. Disease\u2010specific, validated outcome measures should assess function across ages and disease stages. Biomarkers reflecting peripheral nervous system health may serve as surrogate endpoints to support accelerated approval pathways. Patient and care partner perspectives are essential throughout development, particularly regarding treatment goals, risk tolerance, and meaningful endpoints. Successful therapeutic development for CMT and related neuropathies requires innovative approaches that balance rigorous scientific standards with the realities of rare disease research. Regulatory flexibility, informed by patient input and natural history data, can facilitate efficient development while maintaining assurance of safety and effectiveness.<\/jats:p>","DOI":"10.1111\/jns.70146","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:16:28Z","timestamp":1785906988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Development of Therapies for Charcot\u2013Marie\u2013Tooth Disease: Recommendations for Trial Design, Endpoints, and Regulatory Pathways"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1272-9320","authenticated-orcid":false,"given":"Charles K.","family":"Abrams","sequence":"first","affiliation":[{"name":"Department of Neurology and Rehabilitation Chicago College of Medicine, University of Illinois at Chicago  Chicago Illinois USA"},{"name":"Richard and Loan Hill Department of Biomedical Engineering Chicago College of Medicine, University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Bruhn","sequence":"additional","affiliation":[{"name":"Charcot\u2010Marie\u2010Tooth Association  Glenolden Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7936-623X","authenticated-orcid":false,"given":"Joshua","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Cancer Control St. Jude Children\u2019s Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Fleming","sequence":"additional","affiliation":[{"name":"Independent Researcher  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Forsey","sequence":"additional","affiliation":[{"name":"Charcot\u2010Marie\u2010Tooth Association  Glenolden Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-8549","authenticated-orcid":false,"given":"Vera","family":"Fridman","sequence":"additional","affiliation":[{"name":"Department of Neurology Univesity of Colorado Denver School of Medicine  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lin","sequence":"additional","affiliation":[{"name":"Muscular Dystrophy Association  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"McCune","sequence":"additional","affiliation":[{"name":"Scendea Ltd.  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