Calls Now Open
2024 ADDF-Harrington + 2025 Harrington Scholar-Innovator Programs
Neuroscience, Rare/Orphan
Boston Children’s Hospital
Harrington Scholar-Innovator
Rare/Orphan
KCNT1-related epilepsy is an ultra-rare, infant-onset seizure disorder caused by mutations in the KCNT1 gene. Some cases lead to severe seizures that are unresponsive to medications, and encephalopathy, which is a widespread injury of the brain that leads to altered structure and function. Children with KCNT1-related encephalopathic epilepsy typically start missing their normal developmental milestones within months of the seizures beginning, and most never learn to walk or talk.
Dr. Timothy Yu and his team are studying KCNT1 epilepsy through the lens of molecular therapeutic approaches, more specifically through an antisense oligonucleotide (ASO)—short fragments of synthetic RNA/DNA which target the malfunctioning gene. The team’s hypothesis was that if the ASO can encourage cells in the brain to rid themselves of the toxic potassium channel encoded by mutant KCNT1, it can quiet the hyperexcitability of the brain circuits, and allow the patient some respite from their seizures.
After testing the ASOs in patient-derived cells, obtaining promising data in mice and identifying a clinical candidate, Dr. Yu completed the necessary steps to file an IND with the FDA. To date, the ASO has been tested in one patient using intrathecal injection which has demonstrated efficacy in reducing the number and length of seizures.
Since receiving the Harrington Discovery Institute Scholar-Innovator grant in 2020, Dr. Yu has worked to expand the study further and organize a larger scale clinical trial.
“With the Harrington Discovery Institute support, we are really working together collaboratively to come up with models to expand this to a larger trial that we hope to use to enroll more patients and give this promising investigational therapeutic a real solid try.”