Optimizing Therapeutic Control of Epilepsy in Tuberous Sclerosis Complex Using a Novel Biosensor
Abstract
This proposal addresses the Fiscal Year 2022 (FY22) Tuberous Sclerosis Complex Research Program (TSCRP) Focus Area: Preventing epilepsy and improving treatment of tuberous sclerosis complex (TSC)-related seizures. Some of the most important health issues in patients with TSC are neurological disease: autism, intellectual disability, and seizures. More than half of all patients with TSC will develop uncontrolled seizures (epilepsy). The importance of seizure control in TSC cannot be overstated; chronic epilepsy in children is a major risk factor for impaired brain developmental and lifelong disability. The clinical decision-making when a patient is not responding to anticonvulsant medications is complex. To increase the dose to try to achieve a better effect may put the patient at risk for drug toxicity. Non-compliance may be unrecognized and to abandon a medication to begin a trial of a different drug may result in loss of seizure control. There is a significant, unmet clinical need to improve and optimize the dosing of anticonvulsant medications in patients with TSC. Scientific Objective and Rationale: Biosensors act at the intersection between biology and electronics to convert chemical information into electronic signals. We have recently shown that we can accurately measure the level of many drugs used for the treatment of epilepsy directly from the blood using an innovative biosensor. Therapeutic drug monitoring is the clinical practice of measuring medication levels to optimize dosage regimens for patient benefit. It is used to monitor drugs with narrow therapeutic windows and potential toxicity and is based upon on a definable relationship between the concentration of the drug in the blood and its therapeutic effect. An office-based, non-invasive point-of-care medical device that measures the patient’s medication level, from a drop of saliva, during a clinic visit would have a significant impact on patient care to improve seizure control in patients with TSC. Current turnaround time to measure anticonvulsant levels by commercial labs is 2-4 days. The specific aims of this project are to (1) show that we can measure anticonvulsant and other TSC medication levels directly from blood and saliva in the lab and in a large animal model and that the measured levels are as accurate as current laboratory methods, (2) prototype a hand-held medical device to do this, and (3) show that the device can measure the anticonvulsant levels in patients from a drop of saliva taken during a clinic visit. What types of patients will it help, and how will it help them? Sirolimus is a medication used in many patients to reduce tumor growth and to control epilepsy; however, its optimal dose is unknown. Similarly, recent studies have shown that cannabidiol CBD can reduce seizures in children with refractory epilepsy syndromes, and a new CBD drug (Epidiolex) is approved for this use in children. However, little is known about the metabolism of CBD or the optimal dosing of the drug to prevent seizures, and there is no commercial test to measure CBD in the blood. In fact, the therapeutic range for CBD is currently unknown. Management of these patients is challenging and evolving. TSC-associated neuropsychiatric disorder (TAND) is a recent term that describes the clinical spectrum of brain dysfunction in patients with TSC including aggressive behavior, autism spectrum disorder, intellectual disabilities, and psychiatric disorders that require the use of additional medications and treatment strategies to. Current treatment for TAND is expanding to include anti-psychotics, tricyclic antidepressants, and other medications that can be measured using the biosensor. An office-based platform that informs the clinician of the medication level at the time of neurologic and behavioral assessment would improve patient care for seizure control and TAND. What are the potential clinical applications and benefits? The impact of this technology on pat
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310410
Entities
People
- Edward Chaum
Organizations
- United States Army
- Vanderbilt University