Developing a Genetic Risk Prediction Model for Epilepsy in Patients with TSC
Abstract
Focus Areas: (1) Understanding phenotypic heterogeneity in TSC. (2) Developing clinical biomarkers for TSC. Precision medicine is a new era where the risk/treatment plan for common diseases can be assessed based on an individual’s genetic code. This approach can be applied to tuberous sclerosis complex (TSC). TSC is caused by a change in one of two genes, TSC1 or TSC2, causing major medical problems such as seizures (epilepsy) and tumors. However, people with the same change can have very different medical problems. In fact, many times parents do not realize that they themselves have TSC until a child is born with major medical problems such as seizures. If the changes in the TSC1 or TSC2 gene are identical among family members, what is causing these differences in severity? Knowing the answer to this question is important, as it may allow us to treat patients in a more personalized way, reduce patient/family anxiety, and help with family planning. Currently, we cannot predict the patients with TSC who will develop seizures, leaving patients and their families to wonder. Recently, we learned that early control of seizures helps prevent problems with learning and behavior. Since then, researchers have been looking for clinical biomarkers that may help us figure out who we can expect to develop seizures and thus more promptly treat. In the proposed study, we will evaluate genetic differences (modifiers) that put patients with TSC at high or low risk of developing a seizure disorder. Changes in genes associated with seizure will be analyzed in 375 patients with TSC (a large number of samples for a rare disease) using genome-wide arrays that look for small changes in DNA, a method successful in identifying modifiers of other complex diseases. We already have the DNA, consents, and medical information on the patients that will be included in the study. A seizure risk prediction model will be developed based on the identified genetic modifiers, as well as clinical biomarkers that are already known, to give patients a personalized risk of seizures. Two of the four investigators have more than 25 years of experience studying the genetics of TSC and helped find the genes that cause the condition. Another investigator was recruited due to his experience with genome-wide arrays and risk prediction models. The Principal Investigator is a new investigator, who has spent the last 4 years doing TSC research and is highly interested in a lifelong career studying TSC. All patients with TSC and their families may benefit from the study. With the use of an epilepsy risk prediction model, families will better understand what to expect, hopefully reducing anxiety. In addition, treatment plans can be made based on the patient’s specific risk, for example, when/if/what seizure medication and monitoring is needed. This personalized approach can save patients from unnecessary anxiety, doctor visits, testing, and co-pays. It may also help families with tough decisions, such as whether to start or expand a family. The project is expected to take 3 years. Once finished, we will confirm our findings using another set of patients (an agreement is already in place). Therefore, the projected time it may take to be available clinically is 6-8 years. Discovery of genetic modifiers may highlight new molecular pathways that can help identify different medicines to treat TSC. The genetic data generated can also be used to investigate genetic modifiers for other medical problems caused by TSC, such as autism. The genetic data will be shared and can be used in other TSC studies to help the whole research community.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810537
Entities
People
- Laura S Farach
Organizations
- United States Army
- University of Texas Health Science Center at Houston