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Getting STAT -isfaction

delete2025-07-17
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Helen E. Scharfman
DOI：10.1177/15357597251352993delete
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Abstract

Abstract

En 中文
Disease Modification Upon 2 Weeks of Tofacitinib Treatment in a Mouse Model of Chronic Epilepsy Hoffman OR, Koehler JL, Espina JEC, Patterson AM, Gohar ES, Coleman EM, Schoenike BA, Espinosa-Garcia C, Paredes F, Varvel NH, Dingledine RJ, Maguire JL, Roopra AS. Sci Transl Med . 2025;17(790):eadt0527. All current drug treatments for epilepsy, a neurological disorder affecting more than 50 million people, merely treat symptoms, and a third of patients with epilepsy do not respond to medication. There are no disease-modifying treatments that may be administered briefly to patients to enduringly eliminate spontaneous seizures and reverse cognitive deficits. Applying network approaches to whole tissue and single-nucleus transcriptomic data collected from mouse models of temporal lobe epilepsy and publicly available transcriptomic data from human temporal lobectomy samples, we confirmed a previously described pattern of rapid and transient induction of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway within days of epileptogenic insult. This was followed by a resurgent activation of the JAK/STAT pathway weeks to months later with the onset of spontaneous seizures. Targeting the first wave of JAK/STAT activation after epileptic insult did not prevent seizures. However, inhibition of the second wave with CP690550 (tofacitinib) over a 2-week period enduringly suppressed seizures, rescued deficits in spatial memory, and alleviated epilepsy-associated histopathological alterations. Seizure suppression lasted for at least 2 months after the final dose. These results indicate that reignition of inflammatory JAK/signal transducer and activator of transcription 3 signaling in chronic epilepsy opens a window for disease modification with the US Food and Drug Administration-approved, orally available drug CP690550.
Keywords:
epilepsy
tofacitinib
JAK/STAT pathway
disease modification
temporal lobe epilepsy

Journal

Epilepsy Currents cover
Epilepsy Currents
IF:
6.3
Papers:
1.7K
Citations:
1.2K

Organization

No organization information available