Highlights from

AAN 2019

American Academy of Neurology annual meeting

Philadelphia, USA 4-10 May 2019

Leukaemia and hypertension therapies tested in Parkinson's disease

Results of two highly anticipated trials in Parkinson's disease were presented, of therapies already registered for indications outside of neurology. These were the broad-based tyrosine-kinase inhibitor nilotinib, registered for the treatment of chronic myeloid leukaemia (CML) and the dihydropyridine calcium channel antagonist isradipine, an approved treatment of hypertension.

A single dose of nilotinib induced a change of dopamine metabolism in Parkinson’s disease patients [1].“This kind of potential treatment for Parkinson’s could increase the use of a patient’s own dopamine, instead of using or periodically increasing drugs that mimic dopamine”, explained first author Dr Charbel Moussa (Georgetown University Medical Center, Washington DC, USA). In the study she presented, 75 Parkinson’s disease patients were randomised to 5 groups to receive open-label single-dose nilotinib (150, 200, 300, or 400 mg) or placebo. Nilotinib entered the brain in a dose-independent manner. At a dose of 200 mg, nilotinib increased the level of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), which suggests alteration of dopamine metabolism. Nilotinib appeared to significantly reduce the CSF oligomeric:total alpha-synuclein ratio, as well as plasma total alpha-synuclein. The significant increase in the CSF level of triggering receptors on myeloid cells (TREM)-2 which nilotinib induced, suggests an anti-inflammatory effect.

In a phase 3 study, isradipine 10 mg daily failed to slow progression of disability in early Parkinson’s disease [2]. “Still, this study provided us with a lot of valuable information”, said Dr Tanya Simuni (Northwestern Medicine, Chicago, USA). The innovative trial design allowed for the determination of longer duration benefits on clinically relevant outcomes in a relatively small cohort on top of benefits from symptomatic therapy. The 336 participants were randomised to isradipine 10 mg daily or placebo for 3 years. The primary outcome was the change in the Unified Parkinson Disease Rating Scale (UPDRS) Part I-III score measured in the ON state at month 36. This change amounted to 2.99 points in the isradipine group and 3.26 points in the placebo group: a non-significant treatment effect of 0.27 points (P=0.85). Key secondary outcomes showed no statistically significant treatment effect. Isradipine was safe and well-tolerated; the most notable side effect was oedema. “The study recruitment, retention, and compliance were excellent, with a retention rate of 95% in a 3 year study”, Dr Simuni reflected. She speculated that the isradipine dose may have been too low for this indication, the window of opportunity was perhaps already closed, or the calcium channel may not be the leading cause of Parkinson’s disease.

  1. Moussa C, et al. AAN 2019, S10.007.
  2. Simuni T, et al. AAN 2019, Plen02.006.

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