Dose-Response Effect of of Intranasal Insulin Using Functional MRI

Determining the dose response effect of intranasal insulin in humans to optimize the chances for successful translation in settings of TBI


Project at a Glance

Product Type:
Therapeutic

Project Start Date:
7/1/2022

Principal Investigators:
Florian Schmitzberger, MD, MS
Robert Silbergleit, MD
Douglas Noll, PhD

Solution Sheet:
Available soon

Funding History:
$142,939 in non-dilutive funding • 2022 $142,939 Massey Grand Challenge • Substantial departmental, school and center based support


Overview

Insulin acts as a neuroprotective therapy in the brain through multiple signaling mechanisms and can be delivered intranasally. While intranasal insulin has already been studied in human clinical trials of Alzheimer’s dementia and stroke, no previous human studies tested it in TBI or determined its safety and efficacy when given at the high doses shown to be effective in animal TBI models. Therefore a critical knowledge gap in translating intranasal insulin to human TBI clinical trials can be filled by identifying the intranasal insulin dose that achieves the maximum signaling effect in the brain without causing serious side effects.

To optimize the chances for successful translation of intranasal insulin therapy for TBI, the team’s goal is to determine the dose response effect in humans at doses > 160 units. This should be accomplished by utilizing functional MRI in a similar fashion to prior studies.

Insulin molecule, intranasal insulin

Image credit: Shutterstock

Significant Need

Numerous neuroprotective therapies for traumatic brain injury have been demonstrated to be effective in animal models, however all have failed in human clinical trials up to this point.

A major challenge to successful translation is the need to achieve therapeutic drug levels in the brain within a narrow therapeutic window/ timeframe. For traumatic brain injury, the therapeutic window may only last minutes.

Competitive Advantage

Intranasal drug administration takes advantage of known transnasal transport mechanisms to bypass the blood-brain-barrier and rapidly deliver therapeutic agents to the brain within minutes. This delivery method can also be done with minimal training and is utilized frequently and rapidly by laypeople—such as with naloxone to reverse the effects of opioids.

If proven effective in clinical trials, intranasal insulin therapy for TBI could be rapidly implemented in both the civilian prehospital setting and military combat setting.


Funding Organization(s)


Publications

None at this time

Kate Murphy