A groundbreaking study conducted by researchers at the University of Wisconsin–Madison has unveiled the potential of a commonly used arthritis medication to halt brain-damaging seizures in a mouse model resembling epilepsy. The drug in question, tofacitinib, which is typically prescribed to alleviate symptoms of rheumatoid arthritis, demonstrates remarkable efficacy not only in preventing seizures but also in restoring lost cognitive functions and diminishing inflammation within the brain. This discovery could pave the way for a revolutionary treatment for epilepsy, a condition that affects over 50 million individuals worldwide.
Tofacitinib operates by targeting a specific protein known as STAT3, crucial within a cell signaling pathway called JAK. In the context of epilepsy, STAT3’s role has been found to significantly amplify the detrimental activity of neurons during seizures. Prior to this research, it was understood that epilepsy results in a rhythm disruption in brain activity, as neurons begin to fire uncontrollably, leading to dangerous seizures that may cause substantial cell death if left unchecked. Traditional treatments, though they have benefits, often fail to provide relief for approximately one-third of those afflicted by the condition.
The research team, spearheaded by Avtar Roopra, a professor at the UW–Madison School of Medicine and Public Health, and Olivia Hoffman, a postdoctoral researcher, embarked on a systematic investigation employing advanced data science techniques to analyze the gene expression patterns in the brains of mice affected by epilepsy versus those that were not. This meticulous examination unveiled the pivotal role of the STAT3 protein. Further validating the receptors’ relevance, human brain tissue subjected to similar analyses displayed parallel patterns influenced by the STAT3 pathway.
Unexpectedly, during their research, Hoffman stumbled upon a significant correlation between rheumatoid arthritis patients in Taiwan and their incidence of epilepsy. Intriguingly, those receiving long-term treatment with JAK inhibitors exhibited notably reduced epilepsy incidence. This observation propelled the investigation into tofacitinib’s effects, leading to a trial where the mice underwent administration of this JAK inhibitor after being subjected to a brain-damaging agent akin to what simulates epilepsy.
Initially, the results were underwhelming—mice continued to develop epilepsy after the treatment. However, the researchers contemplated a critical aspect of epilepsy: it does not manifest instantaneously following brain injury; rather, there exists a latency period where the brain may appear normal before "reignition" of seizure activity occurs. This pivotal realization prompted the researchers to adjust their approach, administering tofacitinib during this resurgence of seizure activity rather than immediately post-injury.
The outcome was extraordinary. Following a 10-day course of tofacitinib administered at the onset of seizure activity, the researchers observed a surprising cessation of seizures that lasted for two full months. Collaborating institutions, including Tufts University and Emory University, replicated these results in their respective models, signifying the robustness of tofacitinib’s effects across various manifestations of epilepsy.
Remarkably, the prolonged seizure-free period led to substantial recovery in the mice’s cognitive functions, as their ability to navigate mazes returned—a striking improvement reflecting what humans with chronic epilepsy often experience: significant deficits in memory and everyday tasks due to persistent seizure activity. Roopra emphasized the multi-faceted nature of tofacitinib’s impact, noting that it seems to address multiple neurological systems simultaneously, a potential breakthrough in the pharmacological strategy against epilepsy.
Despite tofacitinib’s promising FDA approval for arthritis treatment, transitioning this knowledge into practical applications for human epilepsy patients requires systematic clinical trials. Researchers anticipate that the established safety profile of tofacitinib could expedite this transition, as human consumption of the drug may inherently possess fewer risks due to its prior FDA endorsement.
While awaiting NIH review to facilitate new human studies, Roopra’s lab is focused on unraveling the specific types of brain cells influenced by tofacitinib, intending to expand their investigations into various epilepsy types. Furthermore, Hoffman and Roopra have initiated steps to secure a patent regarding the use of tofacitinib as an innovative disease modifier for epilepsy.
In conclusion, the revelation that a drug previously designated for arthritis could function as an effective therapeutic for epilepsy stands as a testament to the power of interdisciplinary research and innovative thinking in tackling complex health challenges. As epilepsy continues to be a debilitating ailment impacting millions globally, the hope for effective treatments enhances, driven by the promising outcomes witnessed in this groundbreaking study.
Subject of Research: Animals
Article Title: Disease modification upon 2 weeks of tofacitinib treatment in a mouse model of chronic epilepsy
News Publication Date: 19-Mar-2025
Web References: Science Translational Medicine DOI
References: NIH/National Institutes of Health, Lily’s Fund for Epilepsy Research, CURE Epilepsy
Image Credits: Credit: UW–Madison
Keywords: Epilepsy, Seizures, Drug research, Translational medicine, Drug studies
