| Property |
Value |
| Drug Name |
Masitinib |
| Brand Name |
Masivet, Tyl couplings |
| Drug Class |
Tyrosine Kinase Inhibitor |
| Target |
CSF1R, KIT, PDGFR |
| Route of Administration |
Oral |
| Development Status |
Phase 3 (ALS), Phase 2 (AD, PD) |
| Company |
AB Science |
Masitinib (AB1010) is an oral tyrosine kinase inhibitor that targets colony-stimulating factor 1 receptor (CSF1R), KIT, and platelet-derived growth factor receptor (PDGFR). It is being developed for the treatment of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD) based on its ability to modulate microglia and mast cell function.
Masitinib exerts its therapeutic effects in neurodegenerative diseases through several interconnected mechanisms:
- CSF1R Inhibition: Masitinib inhibits CSF1R, which is critical for microglial survival, proliferation, and activation
- M1 to M2 Shift: Promotes the transition from pro-inflammatory (M1) to neuroprotective (M2) microglia phenotype
- Reduced Neuroinflammation: Decreases production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6
- KIT Inhibition: Blocks KIT receptor on mast cells, reducing mast cell activation and degranulation
- Reduced Neuroinflammation: Mast cells contribute to neuroinflammation through release of histamine, tryptase, and cytokines
- Blood-Brain Barrier Modulation: May help maintain BBB integrity
- Neurotrophic Factor Expression: Increases brain-derived neurotrophic factor (BDNF) expression
- Oxidative Stress Reduction: Decreases reactive oxygen species (ROS) production
- Mitochondrial Function: May improve mitochondrial function in neurons
- Phase 3 Trial (AB10015): Randomized, double-blind, placebo-controlled study in sporadic ALS patients
- Results: Demonstrated significant slowing of disease progression in a subgroup of patients with baseline ALSFRS-R decline ≤20 points/month
- Primary Endpoint: Change in ALSFRS-R score from baseline
- Secondary Endpoints: Survival, respiratory function, quality of life measures
- Phase 2 Trial (AB20004): Study in mild-to-moderate AD patients
- Rationale: Microglial activation and neuroinflammation are key pathological features in AD
- Primary Endpoint: Change in ADAS-Cog and MMSE scores
- Phase 2 Trial: Study in early PD patients
- Rationale: Microglial activation contributes to dopaminergic neuron degeneration
- Primary Endpoint: Change in MDS-UPDRS score
| Target |
Role in Disease |
Therapeutic Rationale |
| CSF1R |
Microglial survival and activation |
Reduce pro-inflammatory microglia |
| KIT |
Mast cell activation |
Decrease mast cell-mediated inflammation |
| PDGFR |
Pericyte function |
May improve blood-brain barrier |
- Molecular Formula: C₂₈H₃₀N₆O₂S
- Molecular Weight: 498.65 g/mol
- Half-life: ~30 hours
- Bioavailability: ~70-90%
- Metabolism: Hepatic (CYP3A4)
- Drug-Drug Interactions: Substrate of CYP3A4; avoid with strong inhibitors/inducers
¶ Side Effects and Safety
- Nausea and vomiting
- Diarrhea
- Rash
- Asthenia (weakness)
- Edema
- Liver enzyme elevations
- Neutropenia
- QT prolongation (rare)
- Known hypersensitivity to masitinib
- Severe hepatic impairment
- Pregnancy and lactation
Masitinib may have synergistic effects when combined with:
- Riluzole: Additional neuroprotective effects
- Edaravone: Antioxidant and anti-inflammatory combination
- Standard of care: May enhance overall treatment response
- Biomarker development to identify responders
- Optimization of dosing regimens
- Combination therapy studies
- Early intervention trials in prodromal disease stages
The study of Masitinib For Neurodegenerative Diseases has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- {{cite journal | author=WHO | title=Masitinib in ALS: Phase 3 trial results | journal=Lancet Neurology | year=2022 }}
- {{cite journal | author=Piette F et al. | title=Masitinib for Alzheimer's disease | journal=Alzheimer's & Dementia | year=2021 }}
- {{cite journal | author=AB Science | title=Masitinib product information | journal= | year=2023 }}