How SCN8A gene changes cause severe childhood epilepsy
Functional Genetics of the Neuronal Sodium Channel Gene SCN8A
Working on gene-targeting treatments (AAV, ASO, CRISPR) to reduce seizures in children with SCN8A-related developmental epileptic encephalopathy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Michigan at Ann Arbor NIH-funded |
| Lab location | 1 site (Ann Arbor, United States) |
| Project ID | NIH-11261040 on NIH RePORTER |
What this research studies
Researchers made a mouse that carries the same SCN8A mutation found in some children with developmental epileptic encephalopathy and showed that the mutant channel causes seizures and early death. They previously used an antisense oligonucleotide (ASO) injected into the brain to lower the faulty gene’s messages and delay seizures. Now they are developing more targeted, longer-lasting approaches: AAV-delivered shRNA to limit treatment to specific brain regions and allele-specific CRISPR to inactivate only the mutant copy. They are also studying how the mutation affects cerebellar Purkinje cells to better understand symptoms like ataxia.
Who could benefit from this research
Good fit: Children with confirmed SCN8A mutations that cause developmental epileptic encephalopathy (for example R1872W or N1768D) would be the eventual candidates for these approaches.
Not a fit: People without SCN8A mutations or whose epilepsy is caused by other genes are unlikely to benefit from these SCN8A-targeted approaches.
Why it matters
Potential benefit: If successful, this work could lead to targeted, longer-lasting therapies that reduce seizures and improve survival and quality of life for children with SCN8A-DEE.
How similar studies have performed: Prior preclinical work in this same mouse model showed that ASO treatment reduced seizures and extended lifespan, while allele-specific CRISPR and region-targeted AAV approaches are promising but less established for SCN8A in humans.
Where this research is happening
Ann Arbor, United States
- University of Michigan at Ann Arbor — Ann Arbor, United States (Active)
Researchers
- Principal investigator: Meisler, Miriam H — University of Michigan at Ann Arbor
- Study coordinator: Meisler, Miriam H
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.