Objective: Nilotinib, a tyrosine kinase inhibitor (TKI) was examined with the aim of showing its effect on safety comparing a lower dose of 150mg (N=6) or 300mg (N=6).

Background: Parkinson’s disease (PD) is a neurodegenerative disorder that can affect both cognition and motor functions. Longitudinal change in The Movement Disorder Society-UPDRS (MDS-UPDRS) scores show progressive decline by an average of 6.8 points per year in de novo PD patients.

Methods: We randomized 12 participants with late stage (Hoehn and Yahr 3-5) PD with dementia (PDD) and Lewy body dementia (LBD), who received oral daily doses of Nilotinib for 6 months. Outcomes included measurement of motor and non-motor symptoms using United Parkinson’s disease Rating Scale (UPDRS) I-IV. Montreal Cognitive Assessment (MoCA) in the range of 18-26 was used at screening to determine mild cognitive impairment (MCI), moderate cognitive impairment (17-10) and severe cognitive impairment (<10) in PD and LBD patients. Nilotinib effects on progression of dementia was evaluated using the Mini Mental State Exam (MMSE) and Scales for Outcomes in Parkinson’s disease-Cognition (SCOPA-Cog).

Results: Our results showed that Nilotinib was not only safe, but was also efficacious in a population of patients with such neurodegenerative movement disorders. Although L-Dopa replacement therapy was gradually reduced, Nilotinib significantly improved motor and non-motor functions using United Parkinson’s disease Rating Scale (UPDRS) I-IV and Timed Up and Go. UPDRS I-IV scores improved 7-11 points after 6 months of Nilotinib, suggesting meaningful clinical benefits. In both PDD and LBD patients, MMSE and SCOPA-Cog scores progressively improved (3.85 points and 2 points, respectively) in study participants. Nilotinib also improved speech and language fluency and ameliorated autonomic functions including constipation, urinary incontinence and orthostatic hypotension. The clinical outcomes also correlated with positive movement of relevant CSF biomarkers.

Conclusions: These results indicate that Nilotinib potentially improves both motor, non-motor and autonomic symptoms in PD with dementia and Lewy body Dementia. The data provide feasibility for multicenter, randomized, placebo-controlled, double blind studies in PD and other neurodegenerative diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/nilotinib-improves-motor-skills-cognition-and-autonomic-function-in-open-label-phase-i-clinical-trial-in-parkinsons-disease-with-dementia-and-lewy-body-dementia/