Biomarkers and Future Targets for Development in Amyotrophic Lateral Sclerosis

ISSN: 1875-533X (Online)
ISSN: 0929-8673 (Print)


Volume 21, 38 Issues, 2014


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Current Medicinal Chemistry

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Biomarkers and Future Targets for Development in Amyotrophic Lateral Sclerosis

Author(s): Parvathi Menon, Matthew C. Kiernan and Steve Vucic

Affiliation: Department of Neurology, Westmead Hospital, Cnr Hawkesbury and Darcy Road, Westmead, NSW 2145, Sydney, Australia.

Abstract

Although the pathophysiological mechanisms underlying the development of amyotrophic lateral sclerosis (ALS) remain to be fully elucidated, there have been significant advances in the understanding of ALS pathogenesis, with evidence emerging of a complex interaction between genetic factors and dysfunction of vital molecular pathways. Glutamate- mediated excitoxicity is an important pathophysiological pathway in ALS, and was identified as an important therapeutic biomarker leading to development of the only pharmacologically based disease-modifying treatment currently available for ALS. More recently, a putative role of voltage-gated persistent Na+ channels in ALS pathogenesis has been suggested and underscored by neuroprotective effects of Na+ channel blocking agents in animal models. In addition, advances in ALS genetics have lead to identification of novel pathophysiological processes that could potentially serve as therapeutic targets in ALS. Genetic therapies, including antisense oligonucleotide approaches have been shown to exert neuroprotective effects in animal models of ALS, and Phase I human trial have been completed demonstrating the feasibility of such a therapeutic approach. The present review summarises the advances in ALS pathogenesis, emphasising the importance of these processes as potential targets for drug development in ALS.

Keywords: Amyotrophic lateral sclerosis, clinical trial, excitotoxicity, glutamate, motor neuron disease, riluzole.

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Article Details

Volume: 21
Issue Number: 31
First Page: 3535
Last Page: 3550
Page Count: 16
DOI: 10.2174/0929867321666140601161148
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