Journal article
Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A
Journal of neurology, neurosurgery and psychiatry, Vol.88(11), pp.941-952
11/2017
DOI: 10.1136/jnnp-2017-315721
PMID: 28860329
Abstract
BackgroundCharcot-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.MethodsWe 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.ResultsIn 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.ConclusionsIn 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.
Details
- Title: Subtitle
- Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A
- Creators
- Robert Fledrich - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, GermanyManoj Mannil - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, GermanyAndreas Leha - Department of Medical Statistics, University Medical Center Göttingen (UMG), Göttingen, GermanyCaroline Ehbrecht - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, GermanyAlessandra Solari - Unit of Neuroepidemiology, IRCCS Foundation, C. Besta Neurological Institute, Milan, ItalyAna L Pelayo-Negro - Service of Neurology, University Hospital “Marqués de Valdecilla (IDIVAL)”, University of Cantabria, and “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)”, Santander, SpainJosé Berciano - Service of Neurology, University Hospital “Marqués de Valdecilla (IDIVAL)”, University of Cantabria, and “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED)”, Santander, SpainBeate Schlotter-Weigel - Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, GermanyTuuli J Schnizer - Department of Clinical Neurophysiology, University Medical Center Göttingen (UMG), Göttingen, GermanyThomas Prukop - Institute of Clinical Pharmacology, University Medical Center Göttingen (UMG), Göttingen, GermanyNatalia Garcia-Angarita - Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, GermanyDirk Czesnik - Department of Clinical Neurophysiology, University Medical Center Göttingen (UMG), Göttingen, GermanyJana Haberlová - Department of Child Neurology, Charles University, nd Medical School, University Hospital Motol, Prague, Czech RepublicRadim Mazanec - Department of Child Neurology, Charles University, nd Medical School, University Hospital Motol, Prague, Czech RepublicWalter Paulus - Department of Clinical Neurophysiology, University Medical Center Göttingen (UMG), Göttingen, GermanyTim Beissbarth - Department of Medical Statistics, University Medical Center Göttingen (UMG), Göttingen, GermanyMaggie C Walter - Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, GermanyCMT TRIAAL - CMT-TRIAAL, Milan, ItalyJean-Yves Hogrel - Institute of Myology, GH Pitié-Salpêtrière, Paris, FranceOdile Dubourg - Institute of Myology, GH Pitié-Salpêtrière, Paris, FranceAngelo Schenone - Department of Neurology, Ophthalmology and Genetics, University of Genoa, Genoa, ItalyJonathan Baets - Department of Neurology, Antwerp University Hospital, Antwerpen, BelgiumPeter De Jonghe - Department of Neurology, Antwerp University Hospital, Antwerpen, BelgiumMichael E Shy - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa, USARita Horvath - John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, UKDavide Pareyson - Department of Clinical Neurosciences, Unit of Neurological Rare Diseases of Adulthood, IRCCS Foundation, C. Besta Neurological Institute, Milan, ItalyPavel Seeman - Department of Child Neurology, Charles University, nd Medical School, University Hospital Motol, Prague, Czech RepublicPeter Young - Department of Sleep Medicine and Neuromuscular Diseases, University of Münster, Münster, GermanyMichael W Sereda - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany
- Resource Type
- Journal article
- Publication Details
- Journal of neurology, neurosurgery and psychiatry, Vol.88(11), pp.941-952
- DOI
- 10.1136/jnnp-2017-315721
- PMID
- 28860329
- NLM abbreviation
- J Neurol Neurosurg Psychiatry
- ISSN
- 0022-3050
- eISSN
- 1468-330X
- Grant note
- DOI: 10.13039/501100002426, name: Fondazione Telethon; name: European Leukodystrophy Society; DOI: 10.13039/501100002347, name: Bundesministerium für Bildung und Forschung; DOI: 10.13039/501100003243, name: Ministerstvo Zdravotnictví Ceské Republiky; DOI: 10.13039/100007372, name: Association Belge contre les Maladies Neuro-Musculaires; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft; DOI: 10.13039/501100003197, name: Agenzia Italiana del Farmaco, Ministero della Salute
- Language
- English
- Date published
- 11/2017
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984070550802771
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