Resolution of causality in myotonic dystrophy, type 1 (DM1) via a PATrOL™-enabled therapy


Pre-Clinical Research

Poster Number: 20


Adam Good , Dietrich Stephan PhD


1. Neubase Therapeutics, 2. Neubase Therapeutics

Compelling therapies for DM1 are on the very near-horizon. Ideally the gene-targeted treatment not only fully addresses root causality but has maximal tolerability and easy for patients to take. In DM1, mis-folded DMPK mRNA transcripts in the nucleus sequester critical splice regulators resulting in inappropriate splicing of hundreds of other gene transcripts in patient cells. Neubase has developed a first-in-class "anti-gene" candidate that selectively binds mutant DMPK mRNA, corrects the mis-fold and releases the splice regulators to normalize function. We have demonstrated target engagement of our anti-gene compound in vivo and in vitro, resulting in rapid and broad rescue of mis-splicing across key transcripts without loss DMPK protein. Findings also provide support for the mechanism of action of the anti-gene. This mechanism contrasts with other therapeutic development efforts that explicitly degrade DMPK transcripts to release the sequestered splice regulators, resulting in lowered DMPK protein which appears to have an important function. We believe an anti-gene approach is a unique option for the future treatment of DM1.