Intranasal Insulin Improves Memory in Normal Adults and in Patients with Alzheimer’s Disease

I am the scientist who invented the intranasal insulin treatment that the Obama administration and NIH just announced they would provide millions of dollars in funding to further test and develop for Alzheimer’s disease.

I first developed (US Patent 5,624,898: issued 1997) the non-invasive intranasal method for bypassing the blood-brain barrier to target therapeutics (including insulin) to the brain to treat neurodegenerative disorders such as Alzheimer’s disease and stroke and later expanded the specific use of intranasal insulin to target the brain to treat Alzheimer’s disease and other CNS disorders (US Patent 6,313,093 which is attached to this email). Intranasal peptides, oligonucleotides and small molecule therapeutics bypass the blood-brain barrier and rapidly reach the brain by traveling extracellularly along the olfactory and trigeminal neural pathways. This increases efficacy while reducing systemic exposure and unwanted side effects.

In 2004, Benedict et al. demonstrated that this intranasal insulin treatment improves memory in healthy adults in Germany with no change in the blood levels of insulin or glucose. Over the next several years, the German researchers conducted a total of four human clinical trials showing the that the intranasal insulin treatment I invented improves memory in normal healthy adults.

Some years ago, I approached Dr. Suzanne Craft about my intranasal insulin treatment and encouraged her to conduct a clinical trial in Alzheimer’s patients. In 2006, Dr. Suzanne Craft at the University of Washington and VAMC in Seattle and colleagues (of which I was one), reported that intranasal insulin improved memory in only 20 minutes after a single intranasal insulin treatment in patients with Alzheimer’s disease. In 2008, Dr. Craft and colleagues showed that intranasal insulin (bid) improved memory, attention and functioning in Alzheimer’s disease (AD) patients over a 21 day period, and in September of 2011, Dr. Craft and coworkers reported improved memory and general cognition and reduced loss of brain FDG uptake in patients with AD or amnestic mild cognitive impairment treated in a four month clinical trial with no change in the blood levels of insulin or glucose. Here at the Alzheimer’s Research Center at Regions Hospital and Health Partners, we are now conducting a new trial of intranasal insulin in patients with Alzheimer’s disease using a new form of insulin.

It is not surprising that intranasal insulin is an effective treatment for AD since it has been known for many years that glucose uptake and utiliztion is dramatically decreased in patients with AD based in part on the early work of Dr. Mony de Leon at NYU. Glucose is the only source of energy for brain cells, and the brain cells of AD patients are starved for energy. Alzheimer’s disease has been shown to involve an insulin and IGF-I deficiency and an insulin and IGF-I signaling deficiency in the brain by Eric Steen, Suzanne de la Monte and colleagues in 2005. Dr. De la Monte has referred to Alzheimer’s as Type 3 Diabetes. We also know that type II diabetes is a major risk factor for developing Alzheimer’s disease. Intranasal insulin may even reduce the risk of individuals with diabetes from developing Alzheimer’s disease.

Intranasal insulin is far more than simply a treatment for AD symptoms. When intranasal insulin reaches the brain, it stimulates the formation of insulin degrading enzyme (IDE) which is capable of degrading beta amyloid, one of the principal abnormal proteins known to accumulate in the brains of AD patients. Further, the activity of glycogen-synthase kinase-3-beta, the enzyme that phosphorylates tau to create AD neurofibrillary tangles, has been reported to be down-regulated in response to insulin. Finally insulin receptor signalling increases synaptic density, and loss of synapses is key to the neuropathology of AD. Along with Benedict and colleagues, I have reviewed intranasal insulin as a therapeutic option in the treatment of cognitive impairment in 2011. The final paper demonstrates the effect of intranasal insulin on the stress response in adult men indicating possible use of this treatment for PTSD.

Author’s Bio

Dr. William H. Frey II is the Founder and Director of the Alzheimer’s Research Center at Regions Hospital, Professor of Pharmaceutics and faculty member in Neurology, Oral Biology and Neuroscience at the University of Minnesota and consultant to the pharmaceutical and biotechnology industry.

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