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

Arsh Haj Mohamad Ebrahim Ketabforoush, Rojin Chegini, Shirin Barati, Fatemeh Tahmasebi, Bardia Moghisseh, Mohammad Taghi Joghataei, Faezeh Faghihi, Fereshteh Azedi

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023 Apr

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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. Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Citation

Arsh Haj Mohamad Ebrahim Ketabforoush, Rojin Chegini, Shirin Barati, Fatemeh Tahmasebi, Bardia Moghisseh, Mohammad Taghi Joghataei, Faezeh Faghihi, Fereshteh Azedi. Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023 Apr;160:114378