Objective: Nilotinib is FDA-approved for the treatment of chronic myeloid leukemia (CML) at 800mg oral dose twice daily. We examined the effects of lower doses (less than 50% of CML dose) of Nilotinib on safety and efficacy on a different population: Parkinson’s disease with Dementia and Lewy Body Dementia.

Background: Our pre-clinical data indicate that the tyrosine kinase inhibitor (TKI) Nilotinib improves motor behavior and cognition in several models of neurodegeneration.

Methods: We randomized 12 participants with late stage (Hoehn and Yahr 3-5) PD with dementia (PDD) and Lewy body dementia (LBD) into 150mg (N=6) or 300mg (N=6) groups, who received oral daily doses of Nilotinib for 6 months. Safety data was obtained with emphasis on criteria which included strict monitoring of QTc prolongation, myelosuppression, liver and kidney function as well as other laboratory tests. Patients with cardiovascular complications, long QTc interval and drug contraindications were excluded.

Results: Safety studies demonstrated no significant adverse effects of Nilotinib on QTc prolongation, myelosuppression, laboratory results and orthostatic hypotension. Participants exhibited more common, non-serious adverse events that were very common in the population of older participants including UTIs and pneumonia, suggesting no significant adverse effects of Nilotinib in this study cohort. Nilotinib does not affect QTc range with co-administration medications that are known to cause prolongation of QTc such as SSRIs. Laboratory tests were performed throughout 11 visits according to study protocol, and some were outside the normal range at baseline due to comorbidities that were not exclusionary. Eight participants were able to perform the tilt test. Nilotinib treatment for 24 weeks reduced the average supine drop in blood pressure by 23.25 mmHg in systolic and by 8 mmHg in diastolic.

Conclusions: Our results show that Nilotinib is safe at 150mg and 300mg doses. Interstingly, anecdotal evidence suggest that Nilotinib may have a beneficial effect on constipation, with all 11 study patients reporting more frequent daily bowel movements. Further, the results of this study show that Nilotinib attenuated the drop in systolic and diastolic blood pressure associated with neurogenic orthostatuc hypotension, suggesting a beneficial effect on orthostatic hypotension.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-nilotinib-on-safety-in-open-label-phase-i-clinical-trial-in-parkinsons-disease-with-dementia-and-lewy-body-dementia/