Biomarkers and Validation of Selected Outcome Measures (CMTBiomarker)

Biomarkers and Validation of Selected Outcome Measures (CMTBiomarker)

CMT is a rare disease for which novel treatments are being developed. Evaluation of intervention efficacy is hampered by slow progression and lack of sensitive outcome measures. Primary goal of the project is to identify and validate RNA and protein derived biomarkers in blood of CMT patients for selected outcome measures over 2 years. The investigators expect to develop more responsive outcome measures and circulating biomarkers to improve assessment of intervention efficacy in forthcoming therapeutic trials.

Novel treatments are being developed for CMT. Intervention efficacy evaluation is hampered by slow disease progression and lack of sensitive outcome measures. The investigators have previously shown that biomarkers from skin identified in a CMT1A rat model can be translated to CMT1A patients. Primary goal is to identify circulating biomarkers correlating with disease severity and progression. 210 young, adolescent and adult patients affected by genetically confirmed CMT1A, will be evaluated with different clinical outcome measures, assessing impairment, disability and quality of life: Patients will be re-evaluated at 12 (n=147) and 24 months (n=103) with the same measures to assess disease progression. A number of candidate markers correlating with disease severity have been identified in blood samples from the rat model of CMT1A. At 0-12-24 months a blood sample will be drawn from affected CMT1A patients. The investigators will purify total mRNA from blood samples, and validate the 10 strongest regulated markers identified in the rat model via qRTPCR in blood of CMT1A patients. Protein biomarkers will also be analysed. Marker expression at baseline and at follow up will be correlated with clinical severity and progression. In this translational project (rat/human) the investogators expect to develop more responsive outcome measures and circulating biomarkers to improve assessment of intervention efficacy in forthcoming therapeutic trials.

Inclusion Criteria:

• Clinical diagnosis of CMT1A
• Genetic confirmation of PMP22 duplication (for adults patients)
• Children aged 3-11, adolescents aged 12-17 and adults aged 18-65 years
• Signed informed patient consent

Exclusion Criteria:

• Other causes of neurological and psychiatric disorders
• Severe internistic disease
• Patient known or suspected to be alcohol / drug abuser
• Pregnancy, breast feeding period
• Permanent Vitamin C intake
• Participation an interventional clinical study up to 4 weeks prior to inclusion