# Clinical Trial Readiness for Rare Diseases, Disorders and Syndromes > **NIH NIH R21** · UNIVERSITY OF IOWA · 2020 · $208,750 ## Abstract Abstract: Charcot Marie Tooth disease (CMT) are heritable peripheral neuropathies and are the most common genetic neuromuscular disease, affecting 1:2500 individuals. CMT1A is the most common subtype, affecting approximately 1:4000 patients with CMT, caused by a recurring 1.4 Mb duplication within chromosome 17p11.2 in the region containing the PMP22 gene. CMTX1 (1:25,000), CMT1B (1:36,000) and CMT2A (1:36,000) are the next most frequent forms and are caused by many different mutations in the GJB1, MPZ, and MFN2 genes, respectively. Recent progress on these four forms of CMT has led to clinical trials that have begun or will be ready to begin in the next five years. Clinical trials in humans require sensitive outcome measures (OM) that measure disease progression and target engagements in patients. In the Inherited Neuropathy Consortium (INC) we have generated a number of clinical outcome assessments (COA) to be used in trials for CMT. These include the Rasch modified CMT Neuropathy or Exam Scores (CMTNS-R/CMTES-R), the CMT Pediatric Score (CMTPedS), the CMT Functional Outcome Measure (CMT-FOM), the patient reported CMT Heath Index (CMT-HI) and the CMT infant -toddler scale (CMTInfS). All measure severity and the CMTNS-R/CMTES-R and CMTPedS have detected significant progression in prospective studies over two years. We have also begun development of biomarkers that measure consequences of CMT causing mutations. We have identified that intramuscular fat accumulation (IMFA) increases in calf muscles significantly over one year in patients with CMT1A. We have identified increased levels of neurofilament light (NFL) chains in plasma of patients with multiple CMT subtypes that correlate with disease severity. Preliminary results using Nanostream technology identify increased PMP22 mRNA expression in skin biopsies of patients with CMT1A as well as expression of other Schwann cell specific genes that have been shown to fall with successful treatment in mouse and rat models of CMT1A. In the current proposal we wish to extend our preliminary observations in two Specific Aims: In Aim 1 we will identify correlations between skin PMP22 mRNA, plasma levels of NFL and COA on 60 patients with CMT1A. In Aim 2 we will identify and correlate skin and plasma biomarkers with COA and IMFA levels in leg muscles of 60 subjects with CMT1B, CMTX1 and CMT2A. Taken together results to date suggest that the proposed studies can identify target engagement for potential treatments, markers of demyelination and axonal degeneration and biomarkers that correlate with COA and may be more sensitive to change than the COA in clinical trials. ## Key facts - **NIH application ID:** 9999064 - **Project number:** 5R21TR003034-02 - **Recipient organization:** UNIVERSITY OF IOWA - **Principal Investigator:** MICHAEL E. SHY - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $208,750 - **Award type:** 5 - **Project period:** 2019-08-19 → 2022-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9999064 ## Citation > US National Institutes of Health, RePORTER application 9999064, Clinical Trial Readiness for Rare Diseases, Disorders and Syndromes (5R21TR003034-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999064. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*