Treatment for Epilepsy

University of Kentucky Background
Epilepsy is the 4th most prevalent neurologic disorder after migraine, stroke, and Alzheimer’s disease: affecting 50 million people worldwide and 3.4 million people in the USA have epilepsy and at least 30% of all epilepsy patients are refractory to drug therapy. The prevalence of epilepsy increased since the previous estimate of 3 million people which is thought to be due to population growth. One factor which may influence the incidence of epilepsy in the near future is the expanded definition of epilepsy established by the International League Against Epilepsy (ILAE). According to this definition, diagnosis of epilepsy requires one of the following: 1) two unprovoked seizures occurring at least 24 hours apart; 2) one unprovoked seizure with a high risk of recurrence; 3) diagnosis of an epilepsy syndrome. The latter two characteristics were added to address a patient’s risk of future seizures and help epileptologists in treatment decisions. Living with the threat of future seizures places a significant burden on daily life of epilepsy patients. Only Alzheimer’s disease, stroke, and migraines have higher disability adjusted life years (WHO Neurological Disorders: Public Health Challenges Report). In addition to disease burden, patients with epilepsy (PWE) are frequently afflicted with comorbid neurobehavioral conditions such as depression, suicidal ideation or attempt, cognitive impairment and drug abuse in addition to recurrent seizures.
The current standard of care for treatment of epilepsy involves the use of pharmacotherapy with anti-seizure drugs (ASDs), which act inside the brain on neurons. However, about 30%-40% of patients do not respond to ASDs, and even in patients who respond to ASDs, there are often adverse effects.
Technology Overview
Blood-brain barrier dysfunction is recognized as both a cause and consequence of seizures in epilepsy, yet therapeutic options for restoring barrier function are currently not available. Published findings show that a dysfunctional barrier contributes to seizure genesis and promotes epilepsy progression. University of Kentucky researchers found that a combination drug product (COX-2 and 5-LOX inhibitors) which are already in the market for treating other indications works in a novel pathway and attenuates barrier dysfunction in rodent seizure models.
Stage of Development
Planning potential clinical trial in the future.

Pathway interrupts the positive feedback loop through which seizures drive barrier dysfunction; and
the brain is protected through restoring blood-brain barrier function.
The treatment can also be incorporated into existing treatment approaches, such as use in a combination with anti-seizure drug (ASD) pharmacotherapy, surgery to remove the epileptic focus, and/or vagus nerve stimulation.

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