ArticlePloS one2020
Modulation of KDM1A with vafidemstat rescues memory deficit and behavioral alterations.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Smart Nanomedicines for Neurodegenerative Diseases: Empowering New Therapies with Molecular Imaging and Artificial Intelligence.Molecular diagnosis & therapy · 2026Review
- Inhibition of histone lysine demethylase restores learning and memory in aged mice.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Recapitulation and reversal of neuropsychiatric phenotypes in a mouse model of human endogenous retrovirus type W expression.Molecular psychiatry · 2025Article
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- Review
- Mechanistic insights into novel cyano-pyrimidine pendant chalcone derivatives as LSD1 inhibitors by docking, ADMET, MM/GBSA, and molecular dynamics simulation.Biochemistry and biophysics reports · 2025Article
- Pro-inflammatory S100A8 Protein Exhibits a Detergent-like Effect on Anionic Lipid Bilayers, as Imaged by High-Speed AFM.ACS applied materials & interfaces · 2025Article
- Phenotype and psychometric characterization of Phelan-McDermid syndrome patients: pioneering towards personalized medicine.Frontiers in psychiatry · 2025Article
- Vafidemstat: a lysine-specific demethylase 1A inhibitor that shows promise for treating neuropsychiatric disorders.Epigenetics reports · 2025Article
- Chromatin modifiers in neurodevelopment.Frontiers in molecular neuroscience · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- LPS-induced neuroinflammation induces changes in the transcriptional profile of members of the CoRest repressive complex in the hippocampus.Molecular biology reports · 2024Article
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Transcriptomic dysregulation and autistic-like behaviors in Kmt2c haploinsufficient mice rescued by an LSD1 inhibitor.Molecular psychiatry · 2024Article
- Strategies that regulate LSD1 for novel therapeutics.Acta pharmaceutica Sinica. B · 2024Review
- Review
- A comprehensive AI-driven analysis of large-scale omic datasets reveals novel dual-purpose targets for the treatment of cancer and aging.Aging cell · 2023Article
- Chemical Inhibitors Targeting the Histone Lysine Demethylase Families with Potential for Drug Discovery.Epigenomes · 2023Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription disequilibria are characteristic of many neurodegenerative diseases. The activity-evoked transcription of immediate early genes (IEGs), important for neuronal plasticity, memory and behavior, is altered in CNS diseases and governed by epigenetic modulation. KDM1A, a histone 3 lysine 4 demethylase that forms part of transcription regulation complexes, has been implicated in the control of IEG transcription. Here we report the development of vafidemstat (ORY-2001), a brain penetrant inhibitor of KDM1A and MAOB. ORY-2001 efficiently inhibits brain KDM1A at doses suitable for long term treatment, and corrects memory deficit as assessed in the novel object recognition testing in the Senescence Accelerated Mouse Prone 8 (SAMP8) model for accelerated aging and Alzheimer's disease. Comparison with a selective KDM1A or MAOB inhibitor reveals that KDM1A inhibition is key for efficacy. ORY-2001 further corrects behavior alterations including aggression and social interaction deficits in SAMP8 mice and social avoidance in the rat rearing isolation model. ORY-2001 increases the responsiveness of IEGs, induces genes required for cognitive function and reduces a neuroinflammatory signature in SAMP8 mice. Multiple genes modulated by ORY-2001 are differentially expressed in Late Onset Alzheimer's Disease. Most strikingly, the amplifier of inflammation S100A9 is highly expressed in LOAD and in the hippocampus of SAMP8 mice, and down-regulated by ORY-2001. ORY-2001 is currently in multiple Phase IIa studies.
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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 OpenQuestion graph.