FamilieSCN2A awards $75,000 grant for RNA splicing research

The FamilieSCN2A Foundation has given its 2026 Action Potential Grant to Dutch researcher Dr. Nicky Scheefhals to test an RNA-based approach for reducing neuronal hyperexcitability in SCN2A-related disorders. The project aims to shift SCN2A splicing toward a neonatal exon that acts like a natural brake on brain cell firing, with the goal of reaching more patients than mutation-specific therapies.

Why it matters: - SCN2A-related disorders are severe genetic conditions with few targeted treatment options. - The funded project aims to address a disease mechanism that could apply across multiple SCN2A variants, not just a single mutation. - The approach could move early-stage research toward a broader therapeutic strategy for patients with hyperexcitability-driven seizures and related symptoms.

What happened: - The FamilieSCN2A Foundation awarded its 2026 Action Potential Grant, worth $75,000, to Dr. Nicky Scheefhals. - Scheefhals is a geneticist and neuroscientist at Radboud University Medical Center and the Donders Institute for Brain, Cognition and Behaviour in Nijmegen, Netherlands. - The grant supports her project, "Therapeutic Modulation of SCN2A Exon Switching to Reduce Neuronal Hyperexcitability in SCN2A-related Disorders." - The foundation announced the award on Sept. 11, 2026.

The details: - SCN2A disorders are caused by alterations in the SCN2A gene. - The gene has two mutually exclusive exons: exon 5N and exon 5A. - Exon 5N is expressed mainly during neonatal development. - Exon 5A becomes more prominent as the brain matures into adulthood. - The neonatal variant, exon 5N, requires stronger depolarization to activate. - That makes exon 5N a natural brake on brain cell excitability. - Scheefhals’ strategy uses RNA-based antisense oligonucleotides. - The goal is to shift splicing from adult exon 5A back to protective exon 5N. - Restoring neonatal exon expression is designed to reduce hyperactive sodium channel activity. - The intended effect is to lower neuronal hyperexcitability. - The foundation said the project could help groups of patients rather than addressing mutations one at a time. - The Action Potential Grant program is an investigator-initiated funding mechanism for early-stage, translational research. - The program is designed to support proof-of-concept studies and other high-priority projects that advance disease biology or therapeutic ideas. - Since 2019, the foundation has awarded Action Potential Grants and has invested more than $9.5 million in research since its founding in 2014.

Between the lines: - The project stands out because it uses a natural developmental switch already present in the brain. - That gives the research a broader potential reach than therapies built for individual SCN2A mutations. - Jeffrey Cottrell, Ph.D., the foundation’s interim chief scientific officer, said the approach could become applicable across multiple gain-of-function SCN2A variants if exon shifting meaningfully reduces hyperexcitability. - The foundation is betting that seed funding can produce the proof-of-concept data needed to justify later-stage therapeutic development. - Dr. Scheefhals said the work could open a new therapeutic avenue and that the patient and family community is central to the effort.

What’s next: - Scheefhals will test whether shifting exon usage can reduce neuronal hyperexcitability in SCN2A-related disorders. - The project is expected to generate early proof-of-concept data for future therapeutic development. - If successful, the approach could inform treatments that reach a larger share of the SCN2A patient population.

The bottom line: - The grant backs a strategy that tries to reprogram SCN2A splicing toward a built-in protective state, offering a potentially broader path to treatment than mutation-by-mutation drug design.