Highlights from

AAN 2019

American Academy of Neurology annual meeting

Philadelphia, USA 4-10 May 2019

Leukaemia therapy nilotinib effective in Parkinson’s disease

A single dose of the broad-based tyrosine-kinase inhibitor nilotinib was shown to induce a change of dopamine metabolism in patients with Parkinson's disease (PD). Nilotinib is registered for the treatment of chronic myeloid leukaemia (CML).

“It is exciting because this kind of potential treatment for Parkinson’s increases the use of a patient’s own dopamine instead of using or periodically increasing drugs that mimic dopamine”, commented first author Dr Charbel Moussa (Georgetown University Medical Center, Washington DC, USA). Her group had previously shown that nilotinib penetrates the blood-brain-barrier and potentially improves clinical outcomes in individuals with PD and dementia with Lewy bodies (DLB).

The study presented at the AAN 2019 analysed physiologically-based population pharmacokinetics/pharmacodynamics to determine the effects of nilotinib in a cohort of 75 PD participants. Participants were randomised into 5 groups of 15 each to receive open-label single-dose nilotinib (150, 200, 300, or 400 mg) vs placebo. Plasma and cerebrospinal fluid (CSF) were collected at 1, 2, 3, and 4 hours after nilotinib administration.

The results showed that nilotinib enters the brain in a dose-independent manner. The optimal dose tested was 200 mg, increasing the level of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic Acid (HVA), which suggests alteration of the dopamine metabolism. Nilotinib appeared to significantly reduce CSF oligomeric:total alpha-synuclein ratio, as well as plasma total alpha-synuclein. Furthermore, an anti-inflammatory effect was suggested by the significant increase in the CSF level of triggering receptors on myeloid cells (TREM)-2. Long-term effects of nilotinib will be evaluated in an ongoing phase 2, randomised, double-blinded placebo-controlled study in which patients receive 12 months of treatment with nilotinib 200 mg.

Moussa C, et al. AAN 2019, S10.007.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.