Clinical Outcome Assessments and Biomarkers in Charcot-Marie-Tooth Disease

Area of Science:

• Neurology
• Genetics
• Clinical Trials

Background:

• Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy, with no current disease-modifying treatments.
• Developing effective treatments requires robust clinical outcome assessments (COAs) and biomarkers.

Purpose of the Study:

• To review the challenges and successes in developing and validating COAs and biomarkers for CMT over the past two decades.
• To highlight the evolution of outcome measures and the growing need for objective biomarkers in CMT clinical trials.

Main Methods:

• Review of natural history studies and completed clinical trials in CMT.
• Analysis of limitations of early clinical scales and the development of newer, psychometrically supported scales.
• Evaluation of emerging objective biomarkers, including MRI muscle fat fraction and serum markers.

Main Results:

• Early CMT scales showed limitations; newer scales like CMT neuropathy score version 2 and CMT pediatric scale have been developed.
• MRI muscle fat fraction is a responsive biomarker, but its functional correlation needs further study.
• Serum biomarkers like neurofilament light reliably distinguish CMT patients but require validation for treatment responsiveness.

Conclusions:

• Ongoing clinical trials are testing promising COAs and biomarkers for CMT.
• Establishing optimal combinations of outcome measures and biomarkers is crucial for advancing CMT therapeutics.
• Addressing patient selection and enrollment is vital for the success of upcoming disease-modifying treatment trials in CMT.