Frey, William

Contact Information Email: alzheimr@umn.edu Phone: 651-261-1998

William H. Frey II, Ph.D.
Director, Alzheimer’s Research Center
Professor of Pharmaceutics and Oral Biology
Faculty Member in Neurology and the Neuroscience Program
University of Minnesota

Primary Hospital Affiliation: Regions Hospital / HealthPartners Research Foundation, Saint Paul, MN

Year of Appointment: 1977

Graduate School: Case Western Reserve University, 1975 

William H. Frey II, Ph.D. is Director of the Alzheimer's Research Center at Regions Hospital in St. Paul, MN, Professor of Pharmaceutics and Oral Biology and Faculty Member in Neurology and the Neuroscience Program at the University of Minnesota and consultant to the pharmaceutical and biotechnology industry. His patents, owned by Novartis, Stanford University, HealthPartners Research Foundation and others, target noninvasive delivery of therapeutic agents, including stem cells, to the brain and spinal cord for treating neurological disorders, psychiatric disorders and obesity. Dr. Frey's non-invasive intranasal method for bypassing the blood-brain barrier to target CNS therapeutic agents to the brain while reducing systemic exposure and unwanted side effects has captured the interest of both pharmaceutical companies and neuroscientists around the world. The intranasal insulin treatment he developed for Alzheimer’s disease has been shown in clinical trials to improve memory in both Alzheimer’s patients and normal adults in multiple clinical trials. With over 100 publications in scientific and medical journals, Dr. Frey has been interviewed on Good Morning America, The Today Show, 20/20, All Things Considered and numerous other television and radio shows in the U.S., Europe and Asia. Articles about Dr. Frey's research have appeared in the Wall Street Journal, The New York Times, U.S. News and World Report and other magazines and newspapers around the world. Dr. Frey earned his BA in Chemistry at Washington University in 1969 and Ph.D. in Biochemistry at Case Western Reserve University in 1975.

Brief Summary:

Intranasal insulin, deferoxamine, biopharmaceuticals and therapeutic stem cells bypass the blood-brain barrier to treat Alzheimer’s, stroke, brain tumors, Parkinson’s and other CNS disorders. Intranasal delivery provides a noninvasive, method of bypassing the blood-brain barrier to deliver therapeutic agents to the brain and spinal cord within minutes. It also eliminates the need for systemic administration thereby reducing unwanted systemic side effects. This is possible because of the unique connections that the olfactory and trigeminal nerves provide between the brain and the nasal cavity and external environment. Small molecules, oligonucleotides, enzymes, hormones, other macromolecules and stem cells are rapidly delivered intranasally to the brain. Using this delivery and treatment method, which I first invented in 1989 (US Patent 5,624,898 issued 1997), therapeutic proteins, oligonucleotides and small molecules have been used to treat stroke, Alzheimer’s, brain tumors and other brain disorders in animal models.

The intranasal insulin treatment, which I introduced in both 1989 and later in 1999 (US Patent 6,313,093 issued 2001), has been shown to improve memory in healthy adults and improve memory, attention and functioning in patients with Alzheimer's disease without altering blood levels of insulin or glucose. This is not surprising as Alzheimer's patients have a brain deficiency of insulin, and without insulin, key brain areas are starved for energy and degenerate and amyloid and tau accumulate.

Together with Lusine Danielyan M.D. and colleagues in Germany, we have shown that intranasal stem cells bypass the blood-brain barrier by migrating from the nasal mucosa through the cribriform plate along the olfactory neural pathway into the brain and spinal cord. Using intranasal bone marrow-derived stem cells in animal models, we have shown major improvement in Parkinson’s disease while others have reported improvement in neonatal ischemia. Intranasal delivery is changing the way we treat CNS disorders.

References for further reading:

Frey, W.H.II. (2011) AAPS Newsmagazine 7:14-18 Intranasal Delivery of CNS Therapeutics.

Dhuria, SV, Hanson, LR and Frey, WH II (2010) Journal of Pharmaceutical Sciences 99(4):1654-1673 Intranasal delivery to the central nervous system: mechanisms and experimental considerations.

Helgi B. Schiöth, William H. Frey II, Samantha J Brooks, Christian Benedict (2012) Expert Review of Clinical Pharmacology 5(1):17-20 Insulin to treat Alzheimer’s disease: Just follow your nose?

Hanson, L.R., Roeytenberg, A., Martinez, P.M., Coppes, V.G., Sweet, D.C., Rao, R.J., Marti, D.L., Hoekman, J.D., Matthews, R.B., Frey, W.H.II., Panter, S.S. (2009) JPET 330:679-686. Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke.

Danielyan, Lusine; Schäfer, Richard; von Ameln-Mayerhofer, Andreas; Bernhard, Felix; Verleysdonk, Stephan; Buadze, Marine; Lourhmati, Ali; Klopfer, Tim; Schaumann, Felix; Schmid, Barbara; Koehle, Christoph; Proksch, Barbara; Weissert, Robert; Reichardt, Holger; van den Brandt, Jens; Buniatian, Gayane; Schwab, Matthias; Gleiter, Christoph, Frey, William (2011) Rejuvenation Research 14(1):3-16. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson’s disease.

van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. (2010) Pediatr Res 68:419– 422. Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage.

Benedict, C., Frey W.H.2nd, Schiöth, H.B, Schultes, B., Born, J., Hallschmid, M. (2011) Experimental Gerontology 46(2-3):112-115 Intranasal insulin as a therapeutic option in the treatment of cognitive impairments.

Helgi B. Schiöth, Suzanne Craft, Samantha J. Brooks, William H. Frey II, Christian Benedict (2012) Molecular Neurobiology (In Press; Available online) DOI: 10.1007/s12035-011-8229-6 Brain insulin signaling and Alzheimer`s disease: Current evidence and future directions.