Preliminary findings from a small, proof of concept pilot study using the repurposed cancer drug Nilotinib

Original article: Nilotinib Effects in Parkinson’s disease and Dementia with Lewy bodies, J Parkinsons Dis: July 11, 2016.

The takeaway

The safety and tolerability of Nilotinib, a cancer drug which inhibits one of the pathways leading to dopamine neuron death in animal studies, is put to the test for the first time in a small pilot study in people with Parkinson’s and Lewy Body dementia. Using lower doses, one person out of twelve experienced a heart attack (a serious adverse event (SAE) which is known to occur sometimes in cancer patients treated with Nilotinib) while other adverse events included pneumonia and urinary tract infection. Some improvements in cognition and movement were seen. Future studies with a larger patient group must include a placebo as well in order to establish its safety and tolerability, and ensure that the observed effects are reliably caused by Nilotinib.

Why is it important?

Establishing that Nilotinib is safe and tolerable at these doses in people with Parkinson’s is an essential first step before progressing this drug to a larger, blinded, placebo-controlled trial where its clinical efficacy can be properly put to the test.



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c-Abl (pronounced ‘cable’) is a protein which interferes with the machinery that cleans up toxins and waste products (autophagy), including a-synuclein, in nerve cells. The excessive accumulation of a-synuclein is a hallmark of Parkinson’s, so inhibiting c-Abl should improve the efficiency with which a-synuclein is degraded and so protect dopamine neurons from it.

Nilotinib is a cancer drug which does that, in addition to other functions. Evidence from animal studies has shown that it can reduce the accumulation of a-synuclein, protect dopamine neurons and increase dopamine.

The details

12 people (7 with mid to late Parkinson’s and 5 with Lewy Body dementia) were randomly given either 150 or 300mg Nilotinib orally every day for 6 months, and followed up for another 3 months after the end of the study. These doses of Nilotinib were much lower compared to those given in cancer. The primary outcome measures were safety and tolerability and to this end, neurological and physical examination, as well as ECG and blood chemistry were performed at baseline (before Nilotinib was administered), then every 2 weeks for the first 2 months, and every month thereafter.

At baseline, and at 2 and 6 months, blood samples were taken and lumbar puncture was performed to check the concentration of the drug and c-Abl, dopamine metabolites and a-synuclein in blood and cerebrospinal fluid which is contained in the inner chambers of the brain and bathes the spinal cord (CSF).

Within the 6 month period, some adverse events occurred: one out of the 12 patients taking part had a heart attack, which the authors attributed to an undetected abnormality prior to commencing the study, while another 2 patients showed evidence of adverse changes in heart function. Since Nilotinib can sometimes lead to fatal heart problems in patients with leukemia, more rigorous testing is required. Less serious adverse events included a urinary tract infection and pneumonia requiring hospitalization but which are not uncommon in patients at later stages. Preliminary changes in certain markers of harmful oxidative stress, amyloid and dopamine degradation products, and some improvement in cognition and movement following Nilotinib treatment were observed.

However, since this small study was conducted in very few patients, and importantly, there was no placebo group, or a blinding process, it is difficult to interpret. Since the placebo effect is pronounced in Parkinson’s it is impossible to tell whether the suggested increases in dopamine, cognition and movement were caused by Nilotinib, or the expectation of improvement (placebo effect).

Next steps

A double blinded placebo controlled study is necessary to establish whether Nilotinib is safe and tolerable at these doses, and, whether the improvement in dopamine function on this drug exceeds that seen on placebo.
Original article: Pagan, F., Hebron, M., Valadez, E. H., Torres-Yaghi, Y., Huang, X., Mills, R. R., . . . Moussa, C. July 11, 2016. Nilotinib Effects in Parkinson’s disease and Dementia with Lewy bodies. J Parkinsons Dis, 6(3), 503-517.



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