Calcium Channel Modulation to Prevent Post-Traumatic Epilepsy
Abstract
Epilepsy, with uncontrolled, unprovoked, and recurrent seizures, is a common, disabling, and all too often fatal, long-term consequence of 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 psychiatric (anxiety, depression) and memory problems that compound the disability burden on their life. To control the seizures, patients often are required to take more than one drug. The cumulative effect of taking multiple anti-seizure medications, in addition to the epilepsy and psychiatric comorbidities, create a massive toll on the quality of life of people with epilepsy. To date, no intervention can prevent the development of epilepsy and its associated comorbidities (psychiatric and memory problems). The available treatments cannot control the seizures in more than 30% of the people suffering from post-traumatic epilepsy. In addition, the current available therapies do not improve the anxiety, depression, mobility and memory problems that haunt patients with epilepsy and TBI. Therefore, there is a huge unmet need to prevent the development of epilepsy after TBI. In epilepsy, the current medicines or surgical interventions focus on treating the illness or injury rather than keeping it from happening. However, the ideal in medicine is to prevent a person from developing epilepsy. In this proposal, we hypothesize that a novel treatment could help prevent the development of the symptoms of epilepsy, which means less seizures, and no psychiatric, memory or mobility problems, which will result in a significant improvement in the quality of life of people that suffer epilepsy after TBI. We have preliminary data that shows encouraging evidence that our intervention would be the holy grail for patients that suffer from TBI. The results of this study will prove if this novel approach can become a clinical intervention that can prevent the development of epilepsy after TBI. Similarly, our novel treatment could be the first-ever described to prevent or reverse the 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 prevent epilepsy after TBI using a well-established rat model of the disease. Aim 2 using the same model, we will evaluate if our novel treatment is able to reverse the psychiatric (anxiety), memory and mobility problems associated with epilepsy after TBI. Unlike ever before, we will investigate the severity of psychiatric, cognitive, and neurobehavioral comorbidities in males and females and collect information whether the response to the treatment will show sex dependence. This proposal is particularly unique and innovative as it offers a new approach to help people that suffer this devastating disorder, addressing aspects of the PTE beyond just that of seizures, including cognitive and mental health aspects of the condition. We integrate experts across different disciplines: neuroscience, neuropharmacology, clinical neurology, neuroimaging, and molecular biology. Together, these studies will represent a transformational advancement in understanding the mechanisms that underlie the development of epilepsy after TBI. Findings are anticipated to validate our novel treatment as a therapy to prevent epilepsy and its associated mental health 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
- Jan 04, 2024
- Source ID
- HT94252310354
Entities
People
- Terence O Brien
Organizations
- Monash University
- United States Army