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A consortium of 12 organizations, led by the Ó³»­´«Ã½, has been selected to receive funding from the Advanced Research Projects Agency for Health (ARPA-H) under its THRIVE program. The award, for up to $34.5 million, will fund the Pediatric Epilepsies and Rare CNS (PERC) Gene Editing Platform — a collaboration of academic researchers, clinicians, patient advocates, and biotechnology companies aiming to develop gene-editing treatments for children with rare forms of epilepsy. THRIVE is led by ARPA-H Program Manager Daria Fedyukina, Ph.D.

Developmental and epileptic encephalopathies affect more than three million children worldwide and are caused by mutations across more than 400 different genes. Because any single mutation may affect only a few patients globally, economic incentives for traditional commercial drug development are often missing. The ARPA-H effort is designed to create a platform that shares manufacturing, regulatory precedent, and clinical infrastructure across diseases to address this gap and potentially reach many more patients.

The PERC platform will initially focus on two severe childhood conditions caused by genetic mutations in the brain. The first is Alternating Hemiplegia of Childhood (AHC), a rare disorder caused by mutations in the ATP1A3 gene, in which children experience episodes of temporary paralysis, as well as developmental delays and seizures. The second is Dravet syndrome, caused by mutations in the SCN1A gene, which leads to prolonged, uncontrollable seizures beginning in infancy and can result in lifelong disability or death.

The scientific approach combines gene editing with state-of-the-art vectors for delivery. Precision gene editors — such as base and prime editors — have already reached clinical trials in other organs with promising early results. The PERC team plans to pair these editors with a novel AAV delivery vector called TfR1 CapX, developed at the Ó³»­´«Ã½ and specifically engineered to engage the human transferrin receptor to cross the blood-brain barrier after intravenous infusion without the need for neurosurgery or direct injection into the spinal fluid.

The PERC team has completed significant preparatory work, including demonstrating that their gene-editing approach can rescue animal models of both AHC and Dravet syndrome. TfR1 CapX has been extensively studied preclinically and is expected to have early safety data from human administration later this year.

The collaboration includes the Ó³»­´«Ã½, Boston Children’s Hospital, The Jackson Laboratory, Children’s Hospital Colorado, Children's Hospital of Philadelphia, Apertura Gene Therapy, Viralgen, Rare Epilepsy Network, RARE Hope, and the Dravet Syndrome Foundation. PERC is also part of a broader coalition that includes Critical Path Institute, N=1 Collaborative, Global Genes, Worldwide Clinical Trials, Beam Therapeutics, Prime Medicine, and Mahzi Therapeutics.