CAMBRIDGE, Mass.– Oak Hill Bio, a biotechnology company focused on developing therapies for rare diseases, announced the publication of a peer-reviewed article in Nucleic Acids Research that details the discovery and early preclinical development of rugonersen (OHB-724), an investigational antisense oligonucleotide being developed for Angelman syndrome.
The article, titled “Angelman syndrome patient-derived neuron screen leads to clinical ASO rugonersen targeting UBE3A-ATS with long-lasting effect in monkeys,” outlines how rugonersen was identified through large-scale screening and highlights the preclinical data supporting its clinical development.
Rugonersen was selected after approximately 2,500 LNA-modified antisense oligonucleotides were screened in Angelman syndrome patient-derived neurons, with the candidate showing favorable potency, efficacy, and safety. In nonhuman primates, the therapy demonstrated potent down-regulation of UBE3A-ATS, restoration of UBE3A mRNA and protein in key brain regions, and sustained pharmacology after multiple intrathecal doses, all without adverse effects. Researchers concluded these findings support infrequent dosing in clinical development. Rugonersen also showed superior in vitro potency compared to other antisense oligonucleotides currently in clinical development.
“This tour-de-force research publication highlights the strong scientific foundation for rugonersen’s clinical program,” said Ben Philpot, Ph.D., an Angelman syndrome researcher at the University of North Carolina. “By demonstrating selective UBE3A-ATS knockdown and restoration of UBE3A protein across human patient-derived neurons—and durable effects in nonhuman primates—the work provides a clear translational rationale for rugonersen. We would expect that greater restoration of UBE3A protein would translate into improved therapeutic outcomes.”
