Intranasal Insulin May Improve Motor Functions, Verbal Fluency in Patients With Parkinson Disease

Intranasal insulin (INI) treatment may improve motor skills and verbal fluency in patients with Parkinson disease (PD), according to a new study in PLOS ONE.

The investigators conducted the study to determine the effects of INI on cognition and motor functions in patients with PD. INI treatment was administered with ViaNase, an electronic device that atomized insulin into an inhalable spray that could deliver the drug to the upper nasal cavity olfactory region and easily penetrate the brain.

“In the brain, insulin has vasodilatatory and neurotrophic effects, and therefore INI potential benefits are mediated by other mechanisms than by improving peripheral glycemic control,” researchers wrote. "The effects of INI administration on cognitive performance in patients with PD are yet to be elucidated."

Participants were recruited between August 2014 and September 2015 from the Movement Disorders Clinic at the University of Massachusetts Memorial Medical Center. The single-center phase 2 trial was randomized, placebo-controlled, parallel, and double-blind. A total of 14 patients, 9 male and 5 female, who were diagnosed with and treated for PD completed the study and were included in the analysis. There were 8 individuals in the treatment group and 6 in the control group. Participants were randomly assigned to receive 40 international units of either INI or saline once per day for a period of 4 weeks. Both groups had similar demographic characteristics, disease duration, and levodopa equivalent dose. At baseline, severity of PD and results from neuropsychological tests were also similar between groups.

The trial included a screening visit, a baseline assessment, 2 follow-up visits, and a final treatment assessment. Participants took their usual prescribed medications throughout the study. The last INI or placebo dose was administered on the day of posttreatment assessment.

Researchers conducted the Montreal Cognitive Assessment (MoCA) test to assess symptoms of cognitive impairment. They also administered a verbal fluency (FAS) test, in which participants were asked to name words beginning with the letters F, A, and S over a 1-minute interval to assess phonemic fluency and verbal memory. Researchers used the Beck Depression Inventory to evaluate symptoms of depression.

The Hoehn and Yahr (HY) scale was used to evaluate the severity of PD and determine the effects of treatment; the Unified Parkinson Disease Rating Scale (UPDRS) to determine how PD affected motor, cognitive, and other functions; and a standard 4-meter walking test measured patient walking speed, the number of steps they took, their average stride length, and the time it took to complete the walk.

Those who received placebo had lower FAS, worse HY, and worse UPDRS scores over a period of 1 month. The study found that INI improved verbal fluency, as patients who received the treatment produced more words during the FAS test than the placebo group. The group that received INI also had lower HY disability scores compared with the placebo group and lower UPDRS part-3 motor scores compared with baseline, which suggests that INI can slow disease progression and ease motor symptoms.

Researchers found no differences in MoCA or depression scores at baseline and after treatment between groups. The study also found that results from the 4-meter walking test were unchanged by INI treatment.

Researchers stated that further studies are required to determine whether INI treatment can benefit patients with PD before they develop clinically significant cognitive impairment.

“Our study provided preliminary data that suggested an improvement of functional skills after four weeks of daily INI treatment that paves the way toward a larger cohort study to evaluate long-term safety and potential efficacy of intranasal insulin administration for potential treatment and prevention of functional decline in patients with Parkinson disease,” researchers concluded.

Reference

Novak P, Pimentel Maldonado DA, Novak V. Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: a double-blinded placebo-controlled pilot study. PLoS One. 2019;14(4):e0214364. doi: 10.1371/journal.pone.0214364.