ArticleThe Journal of clinical investigation2021
The matrix metalloproteinase inhibitor IPR-179 has antiseizure and antiepileptogenic effects.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Sarcosine Remodels DNA Methylation-Linked Transcriptional Networks During Epileptogenesis in the Rat Rapid Hippocampal Kindling Model.International journal of molecular sciences · 2026Article
- Zonisamide nanodiamonds for brain targeting: A comprehensive study utilising in silico, in vitro, in vivo, and molecular investigation for successful nose-to-brain delivery for epilepsy management.Drug delivery and translational research · 2026Article
- Review
- Olfactory Mucosa MSCs-Derived Exosomal RPL6 Attenuates Seizure-Induced Neuronal Damage via FGF2-Mediated Oxidative Stress and Mitophagy.Neurochemical research · 2026Article
- The spatial architecture of neuroimmune interactions in epilepsy.Frontiers in immunology · 2026Review
- Pathophysiology of Status Epilepticus Revisited.International journal of molecular sciences · 2025Review
- Review
- Inflammatory proteins as acute biomarkers of post-traumatic epilepsy.Frontiers in neurology · 2025Article
- Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes.Frontiers in pharmacology · 2025Review
- Review
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- Identification of gene regulatory networks affected across drug-resistant epilepsies.Nature communications · 2024Article
- Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication.The Journal of pharmacology and experimental therapeutics · 2024Review
- Matrix Metalloproteinase-9 Contributes to Epilepsy Development after Ischemic Stroke in Mice.International journal of molecular sciences · 2024Article
- Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?World journal of pediatrics : WJP · 2024Review
- Challenges and prospects in geriatric epilepsy treatment: the role of the blood-brain barrier in pharmacotherapy and drug delivery.Frontiers in aging neuroscience · 2024Review
- Blood-CNS barrier dysfunction in amyotrophic lateral sclerosis: Proposed mechanisms and clinical implications.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Article
- The neurovasculature as a target in temporal lobe epilepsy.Brain pathology (Zurich, Switzerland) · 2023Review
- Astrocytes as a target for therapeutic strategies in epilepsy: current insights.Frontiers in molecular neuroscience · 2023Review
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix metalloproteinases (MMPs) are synthesized by neurons and glia and released into the extracellular space, where they act as modulators of neuroplasticity and neuroinflammatory agents. Development of epilepsy (epileptogenesis) is associated with increased expression of MMPs, and therefore, they may represent potential therapeutic drug targets. Using quantitative PCR (qPCR) and immunohistochemistry, we studied the expression of MMPs and their endogenous inhibitors tissue inhibitors of metalloproteinases (TIMPs) in patients with status epilepticus (SE) or temporal lobe epilepsy (TLE) and in a rat TLE model. Furthermore, we tested the MMP2/9 inhibitor IPR-179 in the rapid-kindling rat model and in the intrahippocampal kainic acid mouse model. In both human and experimental epilepsy, MMP and TIMP expression were persistently dysregulated in the hippocampus compared with in controls. IPR-179 treatment reduced seizure severity in the rapid-kindling model and reduced the number of spontaneous seizures in the kainic acid model (during and up to 7 weeks after delivery) without side effects while improving cognitive behavior. Moreover, our data suggest that IPR-179 prevented an MMP2/9-dependent switch-off normally restraining network excitability during the activity period. Since increased MMP expression is a prominent hallmark of the human epileptogenic brain and the MMP inhibitor IPR-179 exhibits antiseizure and antiepileptogenic effects in rodent epilepsy models and attenuates seizure-induced cognitive decline, it deserves further investigation in clinical trials.
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