Eight Northwestern researchers published a study April 29 detailing how RNA therapy could be used before birth to combat a rare form of epilepsy.
The study was published in journal Nature Communications in collaboration with four Boston Children’s Hospital researchers.
Epilepsy is a neurological disorder caused by dysregulated electrical activity in the brain, leading to seizures, uncontrollable muscle movements and muscle convulsions, according to first author and Feinberg research technologist Sean Golinski.
For the type of epilepsy examined in the study — epilepsy of infancy with migrating focal seizures — the mutation in the KCNT1 gene leads to an abnormal KCNT1 protein, causing too much potassium to enter the cells, Golinski said.
KCNT1-related epilepsy affects about 3,000 people worldwide, according to the KCNT1 Epilepsy Foundation.
Antisense oligonucleotide, the treatment used in the study, takes up nucleic acids that bind to the mutated messenger RNA, causing its degradation and lowering production of the subsequent protein that causes this type of epilepsy, Golinski said.
Second-year Feinberg Ph.D. student and study author Karla Soriano said children with this form of epilepsy may experience around 20 or more seizures per day.
“It’s a very ugly disease, very sad,” Soriano said. “Obviously, these kids don’t have a normal development for their life.”
Soriano said the life expectancy of children with the disease is “very short,” with patients usually passing away before they reach age 5 or 6.
Golinski said the paper’s broader impact is exploring the feasibility of treating babies who have the gene mutation before birth.
“The earlier that we can intervene to potentially mitigate the damage caused by these diseases, the better, because when you have a neurodevelopmental disease or disorder, especially when the brain is undergoing its most significant development, it could significantly interfere with brain development and cause irreversible damage,” Golinski said.
A study published April 14 in Nature Medicine, which included some NU and Boston Children’s Hospital authors from the April 29 study, found the antisense oligonucleotide treatment reduced the seizures in two 2-year-old patients with KCNT1-related epilepsy.
The April 29 study found that this treatment could also be used to treat the condition before birth. However, the study used lab-grown neurons, derived from patients with the condition, to analyze the effect of the RNA therapy, Feinberg Prof. Richard Smith said.
Smith, the corresponding author on the April 29 study, said the mutation in the KCNT1 gene affects individuals at random.
“Both you and I have a lot of mutations,” Smith said. “We got lucky that they had fallen in places that are not developmentally relevant.”
Smith said that the majority of experimentation for the study was patch clamp electrophysiology, which Golinski performed in the lab.
“A significant amount of it for me was growing the cells in culture, then letting them grow for a month, then taking those cells, putting them under a microscope,” Golinski said. “Then taking these very, very small microelectrodes and essentially zapping the cells and monitoring or assessing their response to electrical stimuli.”
The study was supported by the National Institute of Neurological Disorders and Stroke and the National Institute of Allergy and Infectious Diseases as well as the Bachrach Family Foundation.
In the future, Smith said this treatment could potentially be expanded to other diseases.
“There are many other genes that are operating in a very similar fashion,” Smith said. “This could end up being almost like a platform-based technology or approach for us to then rinse and repeat with other early-on neurodevelopmental diseases.”
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