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Your search keyword '"for the CMT, Triaal"' showing total 3 results
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3 results on '"for the CMT, Triaal"'

1. Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A

Author

Tim Beissbarth, Pavel Seeman, José Berciano, Radim Mazanec, Jana Haberlová, Jean-Yves Hogrel, Ana L. Pelayo-Negro, Rita Horvath, Robert Fledrich, Michael E. Shy, Peter Young, Walter Paulus, Davide Pareyson, Beate Schlotter-Weigel, Alessandra Solari, Dirk Czesnik, Thomas Prukop, Michael W. Sereda, Angelo Schenone, Maggie C. Walter, Tuuli J. Schnizer, Cmt Triaal, Manoj Mannil, Peter De Jonghe, Odile Dubourg, Natalia Garcia-Angarita, Andreas Leha, Caroline Ehbrecht, Jonathan Baets, and CMT-TRIAAL

Subjects
Male, 0301 basic medicine, Oncology, Pathology, Transcription, Genetic, Biopsy, Messenger, Cathepsin A, Disease, 0302 clinical medicine, Charcot-Marie-Tooth Disease, biomarker, Charcot Marie Tooth disease 1A, disease progression, disease severity, skin biopsy, Adult, Aged, Female, Genetic Markers, Glutathione Transferase, Glycoproteins, Humans, Middle Aged, Neuregulin-1, PPAR gamma, Phosphoric Diester Hydrolases, Prognosis, Pyrophosphatases, RNA, Messenger, Real-Time Polymerase Chain Reaction, Skin, Disease Progression, Treatment Outcome, Surgery, Neurology (clinical), Psychiatry and Mental Health, Medicine, medicine.diagnostic_test, Nuclear Proteins, 3. Good health, Psychiatry and Mental health, Cohort, Biomarker (medicine), Transcription, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Disease cluster, Article, 03 medical and health sciences, Genetic, Internal medicine, business.industry, Therapeutic effect, Clinical trial, 030104 developmental biology, Skin biopsy, RNA, Human medicine, business, 030217 neurology & neurosurgery
Abstract

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.

Published
2017

2. Nerve conduction velocity in CMT1A: what else can we tell?

Author

Manganelli, F, Pisciotta, C, Reilly, Mm, Tozza, S, Schenone, A, Fabrizi, Gm, Cavallaro, T, Vita, G, Padua, Luca, Gemignani, F, Laurà, M, Hughes, Ra, Solari, A, Pareyson, D, Santoro, L, Cmt, Triaal, CMT TRAUK, Group, Padua, Luca (ORCID:0000-0003-2570-9326), Manganelli, F, Pisciotta, C, Reilly, Mm, Tozza, S, Schenone, A, Fabrizi, Gm, Cavallaro, T, Vita, G, Padua, Luca, Gemignani, F, Laurà, M, Hughes, Ra, Solari, A, Pareyson, D, Santoro, L, Cmt, Triaal, CMT TRAUK, Group, and Padua, Luca (ORCID:0000-0003-2570-9326)

Abstract

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT-TRIAAL/CMT-TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A. METHODS: Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot-Marie-Tooth Examination Score (CMTES). RESULTS: NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES. CONCLUSIONS: This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length-dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients.

Published
2016

3. Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A.

Author

Fledrich, Robert, Mannil, Manoj, Leha, Andreas, Ehbrecht, Caroline, Solari, Alessandra, Pelayo-Negro, Ana L., Berciano, José, Schlotter-Weigel, Beate, Schnizer, Tuuli J., Prukop, Thomas, Garcia-Angarita, Natalia, Czesnik, Dirk, Haberlová, Jana, Mazanec, Radim, Paulus, Walter, Beissbarth, Tim, Walter, Maggie C., CMT-TRIAAL, Hogrel, Jean-Yves, and Dubourg, Odile

Subjects
CHARCOT-Marie-Tooth disease, BIOMARKERS, NEUROPATHY, MESSENGER RNA, SKIN biopsy
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2017
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