The most recent kinase being tested in clinical trials is Nilotinib (Tysigna, AMN107), a small molecule Abl inhibitor that is FDA-approved for chronic myeloid leukemia. Abl is a tyrosine kinase that phosphorylates tau on an alternative pathologic site, Tyr394, leading to increased tau aggregation into paired helical fragments. [64] In a small Phase 1/2 trial in patients with Parkinson’s disease dementia (PDD) and dementia with lewy bodies (DLB), nilotinib reduced CSF levels of tau and amyloid in exploratory studies [65]. Based on these results, a Phase 2 trial in 42 patients with mild to moderate AD is underway, with a primary outcome of safety and tolerability (NCT02947893).
