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

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

doi:10.1016/j.biopha.2023.114378

Cited by 27 publications

(11 citation statements)

References 175 publications

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“…As it targets macrophages, mast cells, and microglia cells, masitinib may be useful in treating ALS because it highlights the disease’s neuroinflammatory activity [ 9 ]. Masitinib inhibits the production of inflammatory cytokines, lessens inflammation indirectly, and triggers neuroprotection [ 52 ]. While masitinib shows promise in the treatment of various neurodegenerative disorders, further investigation is necessary to address potential adverse effects and optimize its therapeutic use.…”

Section: Discussionmentioning

confidence: 99%

Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence

Hamad,

Amer,

Hawas

et al. 2023

Neurol Sci

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Objectives Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by modulating key pathways implicated in neurodegeneration. This scoping review aimed to summarize the current evidence of masitinib’s neuroprotective activities from preclinical to clinical studies. Methods This scoping review was conducted following the guidelines described by Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria covered all original studies reporting on the neuroprotective effects of masitinib, including clinical studies, animal studies, and in vitro studies. Results A total of 16 studies met the inclusion criteria and were included in the review. These comprised five randomized controlled trials (RCTs), one post-hoc analysis study, one case report, and nine animal studies. The RCTs focused on Alzheimer’s disease (two studies), multiple sclerosis (two studies), and amyotrophic lateral sclerosis (one study). Across all included studies, masitinib consistently demonstrated neuroprotective properties. However, the majority of RCTs reported concerns regarding the safety profile of masitinib. Preclinical studies revealed the neuroprotective mechanisms of masitinib, which include inhibition of certain kinases interfering with cell proliferation and survival, reduction of neuroinflammation, and exhibition of antioxidant activity. Conclusion The current evidence suggests a promising therapeutic benefit of masitinib in neurodegenerative diseases. However, further research is necessary to validate and expand upon these findings, particularly regarding the precise mechanisms through which masitinib exerts its therapeutic effects. Future studies should also focus on addressing the safety concerns associated with masitinib use.

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Section: Discussionmentioning

confidence: 99%

Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence

Hamad,

Amer,

Hawas

et al. 2023

Neurol Sci

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“…Its beneficial effects on ALS patients have recently been confirmed in a phase 2 randomized trial [ 191 ]. Masitinib, a selective tyrosine kinase inhibitor, downregulates proinflammatory cytokines and modulate neuroinflammation by targeting macrophages, mast cells, and microglia [ 192 ]. Oral Masitinib significantly delays the decline of ALSFRS-R and prolongs survival in ALS patients [ 193 , 194 ].…”

Section: Therapeutic Implicationmentioning

confidence: 99%

The Inflammatory Puzzle: Piecing together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis

Liu

2024

Aging and disease

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that has a complex genetic basis. Through advancements in genetic screening, researchers have identified more than 40 mutant genes associated with ALS, some of which impact immune function. Neuroinflammation, with abnormal activation of immune cells and excessive production of inflammatory cytokines in the central nervous system, significantly contributes to the pathophysiology of ALS. In this review, we examine recent evidence on the involvement of ALS-associated mutant genes in immune dysregulation, with a specific focus on the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and N6-methyladenosine (m 6 A)-mediated immune regulation in the context of neurodegeneration. We also discuss the perturbation of immune cell homeostasis in both the central nervous system and peripheral tissues in ALS. Furthermore, we explore the advancements made in the emerging genetic and cell-based therapies for ALS. This review underscores the complex relationship between ALS and neuroinflammation, highlighting the potential to identify modifiable factors for therapeutic intervention. A deeper understanding of the connection between neuroinflammation and the risk of ALS is crucial for advancing effective treatments for this debilitating disorder.

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“…Moreover, it exhibited a satisfactory safety profile and no severe toxicity on dosing daily at 4.5 or 3.0 mg/kg. Masitinib is a selective tyrosine kinase inhibitor that inhibits proinflammatory cytokines, reducing inflammation and enabling neuroprotection [130]. In a randomized clinical trial, masitinib showed significant benefits over a placebo in reducing the rate of functional decline in ALS patients [131].…”

Section: Alsmentioning

confidence: 99%

Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications

Giri,

Banerjee,

Ghosal

et al. 2024

IJMS

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Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of the total population of the world is affected by some form of NDs, resulting in physical and cognitive disability. The most common NDs include Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Although NDs are caused by a complex interaction of genetic, environmental, and lifestyle variables, neuroinflammation is known to be associated with all NDs, often leading to permanent damage to neurons of the central nervous system. Furthermore, numerous emerging pieces of evidence have demonstrated that inflammation not only supports the progression of NDs but can also serve as an initiator. Hence, various medicines capable of preventing or reducing neuroinflammation have been investigated as ND treatments. While anti-inflammatory medicine has shown promising benefits in several preclinical models, clinical outcomes are often questionable. In this review, we discuss various NDs with their current treatment strategies, the role of neuroinflammation in the pathophysiology of NDs, and the use of anti-inflammatory agents as a potential therapeutic option.

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

Cited by 27 publications

References 175 publications

Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence

Masitinib as a neuroprotective agent: a scoping review of preclinical and clinical evidence

The Inflammatory Puzzle: Piecing together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis

Neuroinflammation in Neurodegenerative Disorders: Current Knowledge and Therapeutic Implications

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