A Prospective Natural History Study Protocol for Clinical Trial Readiness in Synaptic Disorders.
Publication/Presentation Date
2-2-2026
Abstract
OBJECTIVE:
METHODS: Here, we describe a protocol, regulatory structure, and supportive preliminary data for multi-center, prospective natural history studies of
RESULTS: Our data support that existing developmental measures are feasible, informative, and show minimal floor or ceiling effects. Furthermore, we demonstrate that medical record-based seizure history reconstruction reveals unique epilepsy trajectories while minimizing burden to families. We observe disease-specific patterns of developmental performance and distinct longitudinal seizure dynamics, highlighting the need for data generation in a gene/disorder-specific manner for clinical trial readiness.
SIGNIFICANCE: In summary, we present a feasible natural history protocol with prospective data for two complex neurodevelopmental disorders with natural histories that have previously been incompletely characterized, within a regulatory framework that will support the use of these data to expedite clinical trial development.
KEY POINTS:
Published In/Presented At
McKee, J. L., Ruggiero, S. M., Cunningham, K., Coyne, J., McSalley, I., Kaufman, M. C., Bane, B., Chisari, T., Toib, J., Glatts, C., Tefft, S., Orlando, J. M., Padmanabhan, V., Gonzalez, A. K., Harrison, A., Woo, C., Zbikowski, S. A., Dhaduk, R., Mercurio, J., McCarthy, M., … Helbig, I. (2026). A Prospective Natural History Study Protocol for Clinical Trial Readiness in Synaptic Disorders. medRxiv : the preprint server for health sciences, 2026.01.30.26344887. https://doi.org/10.64898/2026.01.30.26344887
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
41674643
Department(s)
Department of Pediatrics
Document Type
Article