Chunk #25 — Therapeutic approaches to toxic tau gain of function — Approach 2: modulate tau post-translational modification (PTM) — O-GlcNAcase inhibitors
Another OGA inhibitor, ASN120290 (ASN-561), has been developed by Asceneuron, with preclinical data in P301S transgenic mice showing a more than two-fold increase in O-GlcNAcylated tau and a decrease in phosphorylated tau. [69] Results from a subsequent Phase 1 trial in 61 healthy controls was announced in 2018, demonstrating safety and tolerability [70]. ASN120290 has since been awarded orphan drug status, and Asceneuron announced in July 2018 that it will enter into Phase 2 clinical trials for the treatment of PSP, though this trial has not yet been initiated.
