Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series.

Autor: Ketabforoush AHME; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran., Chegini R; Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran., Barati S; Department of Anatomy, Saveh University of Medical Sciences, Saveh, Iran., Tahmasebi F; Department of Anatomy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Moghisseh B; Student Research Committee, Arak University of Medical Sciences, Arak, Iran., Joghataei MT; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran., Faghihi F; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: faezefaghihi@yahoo.com., Azedi F; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: azeditehrani.f@iums.ac.ir.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Apr; Vol. 160, pp. 114378. Date of Electronic Publication: 2023 Feb 10.
DOI: 10.1016/j.biopha.2023.114378
Abstrakt: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high mortality and morbidity rate affecting both upper and lower motor neurons (MN). Muscle force reduction, behavioral change, pseudobulbar affect, and cognitive impairments are the most common clinical manifestations of ALS. The main physiopathology of ALS is still unclear, though several studies have identified that oxidative stress, proteinopathies, glutamate-related excitotoxicity, microglial activation, and neuroinflammation may be involved in the pathogenesis of ALS. From 1995 until October 2022, only Riluzole, Dextromethorphan Hydrobromide (DH) with Quinidine sulfate (Q), Edaravone, and Sodium phenylbutyrate with Taurursodiol (PB/TUDCO) have achieved FDA approval for ALS treatment. Despite the use of these four approved agents, the survival rate and quality of life of ALS patients are still low. Thus, finding novel treatments for ALS patients is an urgent requirement. Masitinib, a tyrosine kinase inhibitor, emphasizes the neuro-inflammatory activity of ALS by targeting macrophages, mast cells, and microglia cells. Masitinib downregulates the proinflammatory cytokines, indirectly reduces inflammation, and induces neuroprotection. Also, it was effective in phase 2/3 and 3 clinical trials (CTs) by increasing overall survival and delaying motor, bulbar, and respiratory function deterioration. This review describes the pathophysiology of ALS, focusing on Masitinib's mechanism of action and explaining why Masitinib could be a promising actor in the treatment of ALS patients. In addition, Masitinib CTs and other competitor drugs in phase 3 CTs have been discussed.
Competing Interests: Conflict of interest statement Authors declare no financial and non-financial conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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