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

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 physiopa-thology 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 patho-genesis 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 macro-phages, mast cells, and microglia cells. Masitinib downregulates the proinflammatory cytokines, indirectly re-duces 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 de-scribes 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.

Automated summary

Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative disease affecting upper and lower motor neurons. Despite the approval of a few drugs, the survival rate and quality of life for ALS patients remain low. Masitinib, a tyrosine kinase inhibitor, has shown promising results in clinical trials by targeting neuro-inflammation and inducing neuroprotection. This review discusses the pathophysiology of ALS, the mechanism of action of Masitinib, and its potential as a treatment for ALS, along with other drugs in phase 3 clinical trials.