Reversing Post-Traumatic Epilepsy
Abstract
Epilepsy, with uncontrolled, unprovoked and recurrent seizures, is a common consequence following a traumatic brain injury (TBI), in both the general population as well as in military personnel and Veterans. For those that develop epilepsy, this condition adds a considerable additional disability burden to their lives and risk of mortality. In addition to the seizures, people with epilepsy after TBI also commonly develop significant anxiety, depression, mobility and memory problems that compound the disability burden to their life. To control the seizures, patients often are required to take more than one drug. The cumulative effect of taking multiple anti-seizure drugs, in addition to the epilepsy and psychiatric comorbidities, creates a massive toll on the quality of life of people with epilepsy. However, the available treatments are not able to control the seizures in more than 30% of the people that suffer post-traumatic epilepsy. In addition, the current available treatments do not improve the anxiety, depression, mobility and memory problems that haunt patients with epilepsy and TBI. The only current way to improve the overall symptoms is epilepsy surgery, but this is only available to a small proportion of patients (<5%). The risks, cost, time, and expertise involved in epilepsy surgery, in addition to its limited applicability, make this a less than ideal solution to the problem. There is currently a poor understanding of why epilepsy develops after a TBI in some individuals but not others, so it remains unclear who is most at risk. Identification of this subset of “at-risk” patients would be a major leap forward by allowing for improved prediction of long-term outcomes for patients, as well as the identification of new treatment targets to reduce or reverse epilepsy after TBI. In this proposal, we hypothesize that a novel treatment could help to “reverse” the symptoms of epilepsy, which means less seizures, no psychiatric, memory or mobility problems, which will result in a great improvement in the quality of life of people that suffer epilepsy. We have preliminary data that shows encouraging evidence that our intervention would be the “holy grail” for patients that suffer this devastating condition. The results of this study will prove if this novel approach can become a “surgery in a pill” for patients with epilepsy after TBI but applicable to more people and without the costs, problems, and risks associated with epilepsy surgery. Similarly, our novel treatment could be the first-ever described to reverse psychiatric, memory, or mobility problems in epilepsy after TBI, which until now were thought to be irreversible. Aim 1 of this proposal will test if our novel treatment is able to reverse epilepsy after TBI using a well-established rat model of the disease. In Aim 2, using the same model, we will evaluate if our novel treatment is able to reverse the psychiatric (anxiety, depression, memory and mobility) problems associated with epilepsy after TBI. Aim 3 will look for markers that could help us to understand why epilepsy and the psychiatric problems develop and why these are difficult to treat. This approach will help to personalize the treatment for our patients. This proposal is particularly unique and innovative as it offers a new approach to help people that suffer this devastating disorder. We integrate experts across different disciplines: neuroscience, clinical neurology, and bioinformatics. Together, these studies will represent a transformational advancement in understanding the mechanisms that underlie the development of epilepsy after TBI. Findings are expected to validate our novel treatment as a therapy to reverse epilepsy and its associated psychiatric disorders, with critical implications to improve the quality of life of military, Veterans, and civilian populations.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110925
Entities
People
- Pablo Casillas Espinosa
Organizations
- Monash University
- United States Army