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William H. Frey II, Ph.D. Professor, Department of Neurology, Pharmaceutics, and Oral Biology E-mail: alzheimr@umn.edu Alzheimer's Research Center

Research Interests:

We discovered a simple noninvasive way to deliver nerve growth factors and other therapeutic proteins to the brain. When administered as nose drops, these therapeutic proteins travel directly from the nose into the brain along the olfactory and trigeminal nerves. We and others have shown in animals that not only do these therapeutic proteins rapidly reach the brain by this method, but they are also able to dramatically reduce brain damage from neurologic disease such as stroke and Alzheimer's disease. When nose drops containing insulin-like growth factor-I were given to rats, even several hours after a stroke, brain damage was reduced by 65%, and the rats recovered most of their neurologic function in just a few days. Intranasal insulin-like growth factor-I should be similarly helpful in treating Alzheimer's disease as well, since it can protect cholinergic neurons from damage by beta amyloid and increase acetylcholine. Researchers in Italy have used our intranasal nerve growth factor method to reverse Alzheimer's neurodegeneration in transgenic mice, others in California have demonstrated that intranasal nerve growth factors stimulate neurogenesis in adult animals resulting in new brain cells, we have used an intranasal oligonucleotide to shrink brain tumors and double life-span and others have used intranasal leptin targeted to the hypothalamus to successfully treat obesity in animals.

In collaboration with Dr. Suzanne Craft at the University of Washington , our patented intranasal insulin has been shown to improve memory, attention and cognitive function in patients with Alzheimer's disease. Researchers in Germany have shown our intranasal insulin method improves memory in normal adult humans as well. This new method of targeting drugs to the brain can revolutionize the way we treat neurologic and psychiatric disorders while reducing systemic exposure and side effects of medication.

Additional information is available at the Alzheimer's Center web site www.alzheimersinfo.org . Students and staff with an interest in conducting research should contact Dr. Frey by phone at 651-254-2393 or e-mail at alzheimr@umn.edu .

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.) Dhuria, S.V., Hanson, L.R.,

Frey, W.H. II (2009) JPET 328:312-320 Novel vasoconstrictor formulation to enhance intranasal targeting of neuropeptide therapeutics to the central nervous system.

Hanson, Leah R. and Frey, William H II (2008) BMC Neuroscience 9 Suppl 3:S5 Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease.

Martinez J., Francis G., Liu W., Ramji, N., Pradzinsky, N., Fine J., Wilson, M., Hanson, L.R., Frey, W.H.II , Zochodne D., Gordon T., Toth C. (2008) Neuroscience 157(4):908-925 Intranasal Delivery of Insulin and a Nitric Oxide Synthase Inhibitor in an Experimental Model of ALS .

Reger MA, Watson GS, Green PS, Baker LD, Cholerton B, Fishel MA, Plymate SR, Cherrier MM, Schellenberg GD, Frey II WH , Craft S . (2008) J Alzheimers Dis. 13(3):323-31. Intranasal Insulin Administration Dose-Dependently Modulates Verbal Memory and Plasma Amyloid-beta in Memory-Impaired Older Adults.

Thorne, R.G., Hanson, L.R., Ross, T.M., Frey W.H. II (2008) Neuroscience 152(3):785-797 Delivery of interferon-ß to the monkey CNS following intranasal administration.

Hashizume R., Ozawa T., Gryaznov S.M., Bollen A.W., Lamborn K.R., Frey W.H. II , and Deen D.F. (2008) Neuro-oncology 10: 112-120 New Therapeutic Approach for Brain Tumor: Intranasal Delivery of Telomerase Inhibitor GRN163 into Intracerebral Glioblastoma Xenografts

Ross T., Zuckermann R., Reinhard C., Frey W.H. II (2008) Neurosci. Lett. 439:30-33. Intranasal administration delivers peptoids to the rat central nervous system.

Francis, G., Martinez J., Ramji N., Liu W., Xu K., Fine J., Tuor U., Glazner G., Hanson L.R., Frey, W.H. II , Toth C. (2008) Brain 131:3311-3334 Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in the Diabetic Brain.

Thorne, R.G., Hanson, L.R., Ross, T.M., Frey W.H. II (2008) Neuroscience 152(3):785-797 Delivery of interferon-ß to the monkey CNS following intranasal administration.