Treatment Advances in Parkinson’s Disease and Other Movement Disorders
Pimavanserin (Nuplazid)
Pimavanserin (Nuplazid) has recently been FDA approved for treatment of hallucinations in Parkinson’s disease. It is a 5-HT2A inverse agonist. Pimavanserin blocks the serotonergic receptor and reduces the stimulation effect, causing a decrease in the ability to create hallucinations to the striatal limit. In a 2014 trial, pimavanserin was shown to significantly decrease hallucinations over 43 days. “It is an effective medication … not much in the way of side effects at this point,” said Dr. Kraakevik. “It does have that QT prolongation possibility, so you need to be a little careful in patients who have some cardiac abnormalities or rhythm abnormalities when you use this medication. But otherwise it is relatively well tolerated.”
Therapeutics on the Horizon
Medications in the pipeline include an inhaled carbidopa–levodopa agent (CVT-301). In a randomized controlled trial of 86 subjects, investigators found it to be effective in rapidly reversing “off” symptoms, Dr. Kraakevik reported. “Most of the patients who were in this trial had reversal of their symptoms within about 10 minutes,” he said, adding that CVT-301 should be in phase III studies soon and coming up for approval within the next two years.
Nilotinib was approved by the FDA in 2010 as a treatment for adult patients with a form of chronic myeloid leukemia. Given its mechanism of action as a tyrosine kinase inhibitor, researchers hypothesize that it could be applicable to Parkinson’s disease. In a phase I study involving 12 subjects, investigators found that all of the patients who received nilotinib had a reversible decrease in their Unified Parkinson’s Disease Rating Scale score while also scoring “much better on their Mini-Mental State Examination,” according to Dr. Kraakevik.
“It reversed when the medication was taken away,” he emphasized. “This led to a lot of press and a lot of questions in my clinic, where we are asked … why is not every [therapy] able to do this? And my response to patients is, ‘Right now we have 12 people in an open-label study. We need more data.’”
Such data could come from a double-blind, placebo-controlled clinical trial currently in the planning stages, “but there have allegedly been some disagreements between the key entities about the best way to proceed, and this has slowed the process significantly.”
—Fred Balzac
Suggested Reading
Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014;383(9916):533-540.
Dhall R, Kreitzman DL. Advances in levodopa therapy for Parkinson disease: review of RYTARY (carbidopa and levodopa) clinical efficacy and safety. Neurology. 2016;86(14 suppl 1):S13-S24.
Fox SH. Pimavanserin as treatment for Parkinson’s disease psychosis. Lancet. 2014;383(9916):494-496.
Kaufmann H, Freeman R, Biaggioni I, et al for the NOH301 Investigators. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328-335.
LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord. 2016;31(9):1356-1365.
Pagan F, Hebron M, Valadez EH, et al. Nilotinib effects in Parkinson’s disease and dementia with Lewy bodies. J Parkinsons Dis. 2016;6(3):503-517.
