Masitinib for the treatment of mild to moderate Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a degenerative neurological disorder that is the most common cause of dementia and disability in older patients. Available treatments are symptomatic in nature and are only sufficient to improve the quality of life of AD patients temporarily. A potential strategy, currently under investigation, is to target cell-signaling pathways associated with neurodegeneration, in order to decrease neuroinflammation, excitotoxicity, and to improve cognitive functions. Current review centers on the role of neuroinflammation and the specific contribution of mast cells to AD pathophysiology. The authors look at masitinib therapy and the evidence presented through preclinical and clinical trials. Dual actions of masitinib as an inhibitor of mast cell–glia axis and a Fyn kinase blocker are discussed in the context of AD pathology. Masitinib is in Phase III clinical trials for the treatment of malignant melanoma, mastocytosis, multiple myeloma, gastrointestinal cancer and pancreatic cancer. It is also in Phase II/III clinical trials for the treatment of multiple sclerosis, rheumatoid arthritis and AD. Additional research is warranted to better investigate the potential effects of masitinib in combination with other drugs employed in AD treatment.

Keywords:

• Alzheimer
• inflammation
• masitinib
• neurodegeneration
• tau

Financial & competing interests disclosure

The authors were supported by the project ‘Prometeo’ from SENESCYT (Government of Ecuador). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Current drug treatment of Alzheimer’s disease (AD) is symptomatic and is only effective for a short period of time.

• The amyloid cascade hypothesis has dominated AD research field for decades. However, drugs targeting this pathway have failed.

• Immune response plays a role in AD. Until recently, glial cells were considered to be the main culprits.

• Mast cells contribute to neuroinflammation and participate in the regulation of the blood–brain barrier’s permeability.

• Masitinib, a selective tyrosine kinase inhibitor, blocks c-kit on mast cells.

• Masitinib also targets Fyn kinase, which may contribute to neuroprotection in AD.

• Phase II/III clinical trials with masitinib for the treatment of multiple disorders have been largely successful.

• Masitinib has potential applications in AD treatment.

Notes