Biomarker Development in Focal Cortical Dysplasia
PrincipaI Investigator: Hansel Greiner, MD
Key Personnel: Katherine Holland, MD, PhD, Nancy Ratner, PhD, Kwangmin Choi, Francesco Mangano, DO, FACS, FACOS, Lili Miles, MD, James Leach, MD
Finding the children who will benefit the most from epilepsy surgery is important. Recurring seizures, known as epilepsy, cause worsening brain development and put children at risk for sudden death. When seizure drugs are unable to control seizures, epilepsy surgery to remove the part of the brain causing the seizures is the most effective treatment to improve or cure epilepsy. Our study focuses on a group of children with the most common cause of epilepsy requiring epilepsy surgery—focal cortical dysplasia (FCD). In FCD, a small region of brain is slightly malformed, causing seizures. This area may look normal on imaging in patients. There are two major problems in FCD:
1) The genetic causes are unknown. This prevents any disease-specific treatments from being developed. In rare diseases causing epilepsy, such as tuberous sclerosis complex, there have been major leaps forward in treatment and care following the discovery of the underlying genetic cause.
2) Children with FCD who could benefit from epilepsy surgery cannot be distinguished from other causes of epilepsy.
In this research project, we are studying samples of brain and blood from children requiring epilepsy surgery. Using whole exome sequencing, we are looking for very small changes in the genes that result in epilepsy. We expect these changes will only be present in some of the cells. These changes are called somatic mutations. Finding these somatic mutations is the next step for researchers to find treatments that target the root cause. Until these treatments are available, these same somatic mutations can also be used to identify children with FCD who can benefit from epilepsy surgery. This study has the potential to re-focus research efforts and improve clinical care in FCD, a common and important cause of epilepsy.