Promising Findings: Intranasal Insulin Demonstrates Effective Brain Uptake, Offering Hope for Alzheimer’s Treatment

A new brain imaging study from Wake Forest University School of Medicine has found that intranasal insulin can safely and effectively reach key memory regions of the brain in older adults. The findings, published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, show that this method could be a viable new treatment strategy for Alzheimer’s disease (AD). The study also revealed that insulin absorption patterns varied between individuals with early cognitive decline and those who were cognitively normal.

The Challenge of Treating Brain Diseases

Alzheimer’s disease, a condition affecting an estimated 6.9 million individuals aged 65 and older in the US, is characterized by the buildup of proteins in the form of amyloid plaques and neurofibrillary tangles in the brain. These proteins lead to brain cell death and a gradual shrinking of the brain over time. One of the biggest challenges in developing treatments for such brain diseases is finding a way to get therapeutic agents to the targeted area.

Current antiamyloid antibodies show promise, but they do not address other potential causes of AD, such as insulin dysregulation or impaired neuroplasticity. Previous studies have suggested a link between metabolic and vascular disorders that disrupt insulin regulation and an increased risk of AD. This has led researchers to explore whether treatments for these conditions, like insulin, could be repurposed to help treat AD. Intranasal insulin has previously been shown to reach the brain without altering blood sugar levels and to improve cognition in both human and animal studies.

Study Confirms Brain Uptake and Reveals Key Differences

To further investigate how intranasal insulin reaches the brain, researchers conducted a first-in-human positron emission tomography study with 16 older adults. The participants had an average age of 72, with seven being cognitively normal and nine having mild cognitive impairment. Using a new radiotracer, [68Ga]Ga-NOTA-insulin, and a 6-spray delivery system, the study participants underwent brain and whole-body imaging.

The results demonstrated a high insulin uptake in key memory regions of the brain, including the hippocampus and temporal lobe. A significant finding was that cognitively normal individuals had a higher and more sustained insulin absorption compared to those with mild cognitive impairment. The study also found that, in women, insulin uptake was associated with better cardiovascular health, while a marker of brain amyloid levels was linked to reduced brain absorption.

Safety and Future Outlook

The intranasal treatment was well tolerated by the participants, with only two individuals reporting mild, short-lived headaches. The authors of the study, including Dr. Suzanne Craft, professor of gerontology and geriatric medicine at Wake Forest, noted that these findings are a critical step for developing treatments. Reenal Gandhi, director of business development for Aptar Pharma, which provided the delivery system, called the results a “significant step forward in medicine” that validates their system’s effectiveness.

The study’s authors believe they now have the necessary tools to validate intranasal drug delivery to the brain