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Review
. 2016 Feb;53(2):169-82.
doi: 10.1002/mus.24979. Epub 2015 Dec 29.

ALS biomarkers for therapy development: State of the field and future directions

Michael Benatar  1 , Kevin Boylan  2 , Andreas Jeromin  3 , Seward B Rutkove  4 , James Berry  5 , Nazem Atassi  5 , Lucie Bruijn  6
Affiliations
Review

ALS biomarkers for therapy development: State of the field and future directions

Michael Benatar et al. Muscle Nerve. 2016 Feb.

Abstract

Biomarkers have become the focus of intense research in the field of amyotrophic lateral sclerosis (ALS), with the hope that they might aid therapy development efforts. Notwithstanding the discovery of many candidate biomarkers, none have yet emerged as validated tools for drug development. In this review we present a nuanced view of biomarkers based on the perspective of the Food and Drug Administration; highlight the distinction between discovery and validation; describe existing and emerging resources; review leading biological fluid-based, electrophysiological, and neuroimaging candidates relevant to therapy development efforts; discuss lessons learned from biomarker initiatives in related neurodegenerative diseases; and outline specific steps that we, as a field, might take to hasten the development and validation of biomarkers that will prove useful in enhancing efforts to develop effective treatments for ALS patients. Most important among these is the proposal to establish a federated ALS Biomarker Consortium in which all interested and willing stakeholders may participate with equal opportunity to contribute to the broader mission of biomarker development and validation.

Keywords: ALS; biomarkers; disease progression; pharmacodynamic; predictive; prognostic.

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Conflict of interest statement

Financial Conflicts of Interest

Andreas Jeromin is a paid employee and shareholder of Iron Horse Diagnostics, Inc. Seward Rutkove owns equity, receives consulting fees, and owns patent rights in Skulpt Inc.

Nazem Atassi receives consulting fees from Biogen.

James D. Berry has consulted with Biogen Idec and Neuraltus Pharmaceuticals and has received research support from Voyager Therapeutics, GSK, Cytokinetics, Brainstorm Cell Therapeutics, Novartis, ALS Therapy Development Institute, ALS Association, MDA, and NIH.

References

    1. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clinical Pharmacology and Therapeutics. 2001;69:89–95. - PubMed
    1. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Guidance for Industry and FDA Staff: Qualification Process for Drug Development Tools. 2014.
    1. Shepheard SR, Chataway T, Schultz DW, Rush RA, Rogers ML. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis. PLoS One. 2014;9:e87398. - PMC - PubMed
    1. Katz R. Biomarkers and surrogate markers: an FDA perspective. NeuroRx. 2004;1:189–195. - PMC - PubMed
    1. Atassi N, Berry J, Shui A, et al. The PRO-ACT database: design, initial analyses, and predictive features. Neurology. 2014;83:1719–1725. - PMC - PubMed

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