Intranasal insulin: promising preclinical findings for Parkinson’s

Original article: Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson’s Disease Neuroscience Letters : 2020

The takeaway

A study in a rat model of Parkinson’s has shown that low dose insulin administered through the nose can improve movement and help protect dopaminergic neurons from damage.

Why is it important?

The study builds on previous work in which insulin was administered intranasally to target the brain and counter neurodegeneration, and offers good support for a trial to assess its disease modifying potential in people with Parkinson’s.

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IMPACT

  • Novelty 70% 70%
  • Proximity 60% 60%
  • Deliverability 70% 70%

Impact Opinion

For individuals who do not like needles or have trouble swallowing pills, intranasal delivery of therapeutics represents an efficient means of accessing the brain. This timely pre-clinical study provides a strong case for support for following up a clinical trial that recently reported results (https://www.ncbi.nlm.nih.gov/pubmed/31022213). In that small clinical study, 16 people were assessed over 4 weeks for daily intranasal delivery of insulin, and the treatment was found to be well tolerated. Based on these new results from rodents, a larger clinical trial assessing efficacy seems to be warranted.

Background

Energy balance is vital for neurons to survive, and is thought to be one of the key issues in understanding what causes Parkinson’s. Insulin is a hormone which circulates around the body affecting all cells, including neurons. Its function is to help transport glucose, the fuel they use to function, into neurons. Deficient insulin signaling due to diabetes or the metabolic syndrome often seen with ageing results in a range of effects, including harmful oxidative stress to which dopamine neurons are especially vulnerable. Could administering insulin directly into the brain improve their survival?

The details

The researchers used a specially developed tool – called the POD (Precision Olfactory Delivery) device – to deliver insulin into the upper third of the nasal cavity, which is separated by a porous bony surface at that point in the skull, from the brain. Given the right equipment, intranasal drug delivery can be highly effective and quick, without impact on or processing by the rest of the body.

The team separated 39 rats into three groups. Two groups of rats underwent surgery to deliver a toxin directly into the brain, in order to mimic Parkinson’s. They were compared to a third group that only received the surgery required to deliver the toxin, but not the toxin itself, to check that the animal model was successful in recreating many of the symptoms caused by Parkinson’s. In the two animal model groups, rats were treated intranasally either with a) plain saline, or b) with a low dose of insulin.

After 4 weeks of daily (Monday through Friday) dosing, all the animals underwent behavioural testing and the researchers also checked on the survival of dopamine neurons. As expected, the toxin caused movement problems and reduced the number of dopamine neurons in the group that received the toxin and daily saline, compared to the group that only had the sham surgery and saline. The intranasal insulin group performed better on two tests of balance and movement, and also had improved dopamine neuron survival.

Next steps

The exact mechanism by which insulin helped neurons survive in this animal model were not investigated, but this low dose of insulin was well tolerated. A double blind randomized placebo controlled study in a very small number of people with Parkinson’s has already shown promising results in terms of cognition and movement after a month of intranasal insulin. A larger and potentially longer trial assessing safety, tolerability and the optimal dose of both the device and insulin is an important future step.

Related work and trials

Intranasal insulin in people with Parkinson’s
https://clinicaltrials.gov/ct2/show/NCT02064166

Where can I learn more?

https://www.parkinsonsmovement.com/insulin-resistance/

Exosomes as new biomarker

Diabetes drug slows progression in lab

Metabolic syndrome increases PD risk

https://www.parkinsonsmovement.com/nasal-delivery-of-exenatide/

Fine, JM, Stroebel, BM, Faltesek, KA, Terai, K, Haase, L, Knutzen, KE, Kosyakovvsky, J, Bowe, TJ, Fuller, AK, Frey, WH, Hanson LR. (2020). Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson’s Disease
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