Treatment with Intranasal Insulin May Improve Verbal Fluency and Motor Function, Early Study Shows

Treatment with intranasal insulin — which is atomized into a spray and inhaled through the nose — may ease Parkinson’s disease-related cognitive impairment and motor symptoms without dangerously lowering blood sugar levels, according to a proof-of-concept trial.

The study, “Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: A double-blinded placebo-controlled pilot study,” was published in PLoS ONE.

Insulin, which regulates sugar (glucose) levels in the blood, is known to have potent effects in the brain, including on cognition. Intranasal insulin treatment has been shown to increase functional connectivity in the brain in type 2 diabetes without changing serum glucose levels.

Evidence also indicates that intranasal insulin improves visuospatial (visual perception of the spatial relationships between objects) and verbal short-term memory in people with mild cognitive impairment due to Alzheimer’s disease.

Cognitive impairment is a common non-motor complication of Parkinson’s disease. However, the effects of intranasal insulin on this particular complication remain to be understood.

In this study, researchers from Harvard Medical School and University of Massachusetts designed a randomized, placebo-controlled, single-center Phase 2 trial (NCT02064166) to evaluate the effectiveness of intranasal insulin as a treatment for individuals with Parkinson’s and multiple system atrophy (MSA). The symptoms of MSA are similar to those seen in Parkinson’s, but the disorder has a quicker progression and a much shorter survival rate.

A total 14 patients, comprised of nine men and five women, were randomly assigned to receive 40 international units (IU) of intranasal insulin or saline once daily for four weeks. Nine individuals were included in the insulin group and the remaining six were allocated to the placebo group.

Participants were diagnosed and treated for Parkinson’s disease, with one subject in the insulin group also treated for possible multiple system atrophy.

During the trial, participants completed a screening visit, a baseline assessment, two follow-up visits, and an end-of-treatment assessment. Researchers performed neuropsychological testing, and evaluated patients’ motor function — using several disease severity scales and a walking test — and disease progression.

Participants kept taking their usual medications. The last intranasal insulin or placebo dose was given on the day of post-treatment assessment.

The intranasal therapy was safe and well-tolerated and there were no treatment-related side effects. Importantly, blood glucose levels remained normal in treated individuals.

Results revealed patients who received the insulin had better verbal fluency than those given the placebo. Compared with their pre-treatment assessments, individuals given insulin also had decreased disease severity and motor scores — indicating their motor symptoms were eased by treatment and that the Parkinson’s did not progress as fast.

Interestingly, the patient with probable multiple system atrophy, who was included in the insulin group, remained stable during the study and showed a tendency toward improvement of motor skills.

“Although this is a single case of INI [intranasal insulin] treatment in MSA [multiple system atrophy], it warrants further investigation as there are no therapies available to modify disease progression,” the researchers said.

No changes were observed in cognitive, depression, or gait assessments within and between groups.

“Our study provided preliminary data that suggested an improvement of functional skills after four weeks of daily INI [intranasal insulin] 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,” the study concluded.