Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Parkinson's Disease
Status:
Unknown status
Trial end date:
2020-07-01
Target enrollment:
Participant gender:
Summary
Parkinson's disease (PD) is the second most common neurodegenerative disorder causing motor
and non-motor symptoms. PD is characterized by death of dopaminergic (DA) neurons in the
substantia nigra (SN) pars compacta and formation of inclusions known as Lewy bodies (LBs)
that primarily contain aggregated alpha-Synuclein. Nilotinib (Tasigna®, AMN107, Novartis,
Switzerland) is approved by U.S. Food and Drug Administration (FDA) and is well tolerated for
CML treatment at oral doses of 600-800mg daily. Nilotinib penetrates the brain and promotes
autophagic degradation of alpha-Synuclein and p-Tau, leading to survival of DA neurons and
improvement of motor function in PD models. For these studies, Nilotinib (1-10mg/kg daily)
was used at significantly less than the clinically approved dose (up to 1200mg daily) in CML.