ArticleScience translational medicine2023
The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson's disease.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson's disease.Nature aging · 2026Trial
- A Phase I, Randomized, SAD, MAD, and PK Study of Risvodetinib in Older Adults and Parkinson's Disease.Journal of Parkinson's disease · 2024Trial
- XunZi, an AI biologist, reveals disease-modifying targets.Nature biomedical engineering · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Parkinson's disease: pathogenesis and therapeutic strategies.Molecular biomedicine · 2026Review
- Discovery of multitargeting single agents as a novel route to the potential treatment of neurodegenerative diseases.Bioorganic & medicinal chemistry letters · 2026Article
- Evaluation of Additive Neuroprotective Effect of Combination Therapy for Parkinson's Disease Using In Vitro Models.Antioxidants (Basel, Switzerland) · 2025Article
- Preclinical studies and transcriptome analysis in a model of Parkinson's disease with dopaminergic ZNF746 expression.Molecular neurodegeneration · 2025Article
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- An update on novel and emerging therapeutic targets in Parkinson's disease.Metabolic brain disease · 2024Review
- Review
- The Mechanisms of the Roles of α-Synuclein, Amyloid-β, and Tau Protein in the Lewy Body Diseases: Pathogenesis, Early Detection, and Therapeutics.International journal of molecular sciences · 2023Review
- Natural Products as the Potential to Improve Alzheimer's and Parkinson's Disease.International journal of molecular sciences · 2023Review
- Suppressing c-Abl in Parkinson disease.Nature reviews. Drug discovery · 2023Article
- Alpha synuclein post translational modifications: potential targets for Parkinson's disease therapy?Frontiers in molecular neuroscience · 2023Review
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19 authors at 2 institutions in 1 country.
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Abstract
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system, with an estimated 5,000,000 cases worldwide. PD pathology is characterized by the accumulation of misfolded α-synuclein, which is thought to play a critical role in the pathogenesis of the disease. Animal models of PD suggest that activation of Abelson tyrosine kinase (c-Abl) plays an essential role in the initiation and progression of α-synuclein pathology and initiates processes leading to degeneration of dopaminergic and nondopaminergic neurons. Given the potential role of c-Abl in PD, a c-Abl inhibitor library was developed to identify orally bioavailable c-Abl inhibitors capable of crossing the blood-brain barrier based on predefined characteristics, leading to the discovery of IkT-148009. IkT-148009, a brain-penetrant c-Abl inhibitor with a favorable toxicology profile, was analyzed for therapeutic potential in animal models of slowly progressive, α-synuclein-dependent PD. In mouse models of both inherited and sporadic PD, IkT-148009 suppressed c-Abl activation to baseline and substantially protected dopaminergic neurons from degeneration when administered therapeutically by once daily oral gavage beginning 4 weeks after disease initiation. Recovery of motor function in PD mice occurred within 8 weeks of initiating treatment concomitantly with a reduction in α-synuclein pathology in the mouse brain. These findings suggest that IkT-148009 may have potential as a disease-modifying therapy in PD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.