Phosphorylated neurofilament heavy chain: a biomarker of survival for <i>C9ORF72</i>-associated amyotrophic lateral sclerosis

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Abstract

As potential treatments for C9ORF72-associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions. These data support the use of CSF pNFH as a prognostic biomarker for clinical trials, which will increase the likelihood of successfully developing a treatment for c9ALS.

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Journal

Journal ID (nlm-journal-id): 7707449

Journal ID (pubmed-jr-id): 656

Journal ID (nlm-ta): Ann Neurol

Journal ID (iso-abbrev): Ann. Neurol.

Title: Annals of neurology

ISSN (Print): 0364-5134

ISSN (Electronic): 1531-8249

Publication date Nihms-submitted: 3 November 2017

Publication date (Print): July 2017

Publication date PMC-release: 01 July 2018

Volume: 82

Issue: 1

Pages: 139-146

Affiliations

[1 ]Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA

[2 ]Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA

[3 ]Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL 32224, USA

[4 ]Department of Neurology, University of Miami, Miami, FL 33136, USA

[5 ]Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA

[6 ]Department of Neurology, University Hospital Mútua de Terrassa, and Research Foundation Mútua de Terrassa, University of Barcelona, Terrassa, Barcelona, Spain

[7 ]Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

[8 ]Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA

[9 ]Department of Neurology and the Penn Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA 19104, USA

[10 ]Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA 02114, USA

[11 ]Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA

[12 ]Department of Neurology-Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy

[13 ]Department of Pathophysiology and Transplantation, 'Dino Ferrari' Centre – Università degli Studi di Milano, Milan, Italy

[14 ]Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA

[15 ]Motor Neuron Disorders Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA

[16 ]Iron Horse Diagnostics, Inc. Scottsdale, AZ 85255, USA

[17 ]Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA

Author notes

[* ]To whom correspondence should be addressed: Leonard Petrucelli, PhD, Department of Neuroscience, Mayo Clinic Florida, Telephone number: +1 904-953-2855, Fax number: +1 904-953-6276, Petrucelli.Leonard@ 123456mayo.edu , Tania Gendron, PhD, Department of Neuroscience, Mayo Clinic Florida, Telephone number: +1 904-953-6414, Fax number: +1 904-953-6276, Gendron.Tania@ 123456mayo.edu

Article

Accession ID: PMC5676468 Pmcid ID: PMC5676468 Pmc-uid ID: 5676468 Manuscript ID: nihpa886386

DOI: 10.1002/ana.24980

PMC ID: 5676468

PubMed ID: 28628244

SO-VID: 2f5811d7-f31a-4103-aa9f-9a7b0a18b499

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Phosphorylated neurofilament heavy chain: a biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis

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