November 9, 2023
In a recent study published in Nature Genetics, Erin Heinzen, Pharm.D. ‘01, Ph.D. ‘04, in collaboration with Nationwide Children’s Hospital, found a new cause of brain mosaicism and focal epilepsy, which could one day lead to better treatments. Dr. Heinzen is an associate professor at the UNC Eshelman School of Pharmacy in the Division of Pharmacotherapy and Experimental Therapeutics (DPET) with a joint appointment in the UNC Department of Genetics. Her research broadly focuses on neurodevelopmental disease genetics.
Most genetic variants present in the cells that make up our body are inherited from our parents. Although, as cells divide during development, genetic variants can be newly acquired or even sometimes lost. When this happens we become a mosaic, with some cells having slightly different genomes than other cells. In some cases, the groups of cells with a unique genomic makeup can be restricted to certain tissues like the brain. “There’s a lot of evidence that shows that mosaicism in the brain can cause epilepsy or seizures,” Heinzen said.
Seizures can affect the entire brain or just a region. Localized seizures are difficult to manage with medications, and often the only remaining treatment option is to remove that region of the brain through surgery. “Our research seeks to identify the specific genetic variants that cause localized seizures by studying mosaic brain tissue removed from patients during surgery,” Heinzen explained.
This study identified six individuals whose seizures are caused by extra copies of a large part of chromosome 1. The chromosomal abnormality was present only in a subset of brain cells removed during surgery. This genetic change has not been seen in individuals without epilepsy and is also absent from cells collected from the blood.
“What was particularly interesting was that the extra pieces of the chromosome were inherited from the mother and then lost in most cells during embryonic development. The cells with the extra copies of part of chromosome 1 persisted in astrocytes, cells that support neurons in the brain.” Heinzen said. Neuropathologists involved in this study found that all of these cases had abnormal astrocytes in the region where the extra parts of chromosome 1 were found.
“These findings add to our understanding of genetic causes of epilepsy which we hope will help us identify new and better ways to stop seizures in these individuals,” Heinzen said.
A step in the right direction of finding more effective treatments for epilepsy, Heinzen is excited about the new research avenues that are opened by this work. She mentioned that the genetic cause of seizures remains unknown in 70% of children with epilepsy who undergo surgery to manage their seizures, underscoring the need for further research.
Meethila Gade, Ph.D. candidate in DPET and Heinzen lab member was also an author of the study.
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