RT Journal Article
SR Electronic
T1 Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 941
OP 952
DO 10.1136/jnnp-2017-315721
VO 88
IS 11
A1 Robert Fledrich
A1 Manoj Mannil
A1 Andreas Leha
A1 Caroline Ehbrecht
A1 Alessandra Solari
A1 Ana L Pelayo-Negro
A1 José Berciano
A1 Beate Schlotter-Weigel
A1 Tuuli J Schnizer
A1 Thomas Prukop
A1 Natalia Garcia-Angarita
A1 Dirk Czesnik
A1 Jana Haberlová
A1 Radim Mazanec
A1 Walter Paulus
A1 Tim Beissbarth
A1 Maggie C Walter
A1 CMT- TRIAAL
A1 Jean-Yves Hogrel
A1 Odile Dubourg
A1 Angelo Schenone
A1 Jonathan Baets
A1 Peter De Jonghe
A1 Michael E Shy
A1 Rita Horvath
A1 Davide Pareyson
A1 Pavel Seeman
A1 Peter Young
A1 Michael W Sereda
YR 2017
UL http://jnnp.bmj.com/content/88/11/941.abstract
AB Background Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited neuropathy, a debilitating disease without known cure. Among patients with CMT1A, disease manifestation, progression and severity are strikingly variable, which poses major challenges for the development of new therapies. Hence, there is a strong need for sensitive outcome measures such as disease and progression biomarkers, which would add powerful tools to monitor therapeutic effects in CMT1A.Methods We established a pan-European and American consortium comprising nine clinical centres including 311 patients with CMT1A in total. From all patients, the CMT neuropathy score and secondary outcome measures were obtained and a skin biopsy collected. In order to assess and validate disease severity and progression biomarkers, we performed qPCR on a set of 16 animal model-derived potential biomarkers in skin biopsy mRNA extracts.Results In 266 patients with CMT1A, a cluster of eight cutaneous transcripts differentiates disease severity with a sensitivity and specificity of 90% and 76.1%, respectively. In an additional cohort of 45 patients with CMT1A, from whom a second skin biopsy was taken after 2–3 years, the cutaneous mRNA expression of GSTT2, CTSA, PPARG, CDA, ENPP1 and NRG1-Iis changing over time and correlates with disease progression.Conclusions In summary, we provide evidence that cutaneous transcripts in patients with CMT1A serve as disease severity and progression biomarkers and, if implemented into clinical trials, they could markedly accelerate the development of a therapy for CMT1A.