Epilepsy is one of the most common neurological diseases, affecting more than 50 million people worldwide. Although its causes are numerous, the disease often appears after a brain injury, such as physical shock or stroke. A few days, months, or even years after the lesion, the brain loses its ability to “stay calm”. The brain electrical activity is disrupting, neurons are activated permanently and synchronously. This causes crises that can lead to massive cell death.
The candidate drug in question is generally prescribed against arthritis. His repositioning in the treatment of epilepsy made his first proof of concept, in the model mice of the disease. The drug, called tofacitinib, also restores – always in mice model – memory lost due to epilepsy and reduces brain inflammation caused by the disease. If the effectiveness of the drug was demonstrated in humans, its effectiveness would exceed that of current drugs, with a lasting reducing effect of crises, even after stopping treatment.
The main author, Dr. Avtar Roopra, professor of neuroscience at the University of Wisconsin-Madison sums up:
“This medication meets all our criteria”.
The study Evaluates the potential of tofacitinib in the treatment of epilepsy, using methods capable of analyzing the way thousands of genes are expressed in millions of brain cells of epileptic and non -epileptic mice. This methodology here makes it possible to identify:
-- A protein called stat3, key to a cell signaling path called JAK, at the heart of the brain activity of mice with crises;
- A similar analysis of data from brain tissue taken from epileptic humans, also confirms the involvement of stat3;
- Another study reveals a higher prevalence of epilepsy in arthritic participants but surprisingly less than normal in arthritic patients taking anti-inflammatory drugs for more than 5 years.
Explication : In the event of rheumatoid arthritis for several years, the doctor frequently prescribes a Jak inhibitor, a drug that targets this signaling path, also essential in epilepsy.
Proof of concept: Here, the administration of Tofacitinib, a Jak inhibitor, just after the administration of a drug damaging the brain and causing repeated crises had no effect. Mouses have still developed epilepsy like human patients.
However, a 10 -day treatment of tofacitinib, started from the first crises in these mice models of epilepsy, works better than expected : after this 10 -day treatment, the mice remained Without crisis for 2 months. In addition, the cognitive functions have also recovered, “What is amazing”comment on the authors. The drug – the effectiveness should be validated in humans – seems to act simultaneously on several brain systems to control everything, unlike drugs that only target a symptom.
Tofacitinib being already approved for the treatment of arthritis, its repositioning in the treatment of epilepsy could be relatively rapid.
