William H. Frey II, Ph.D.

Professor, Department of Neurology, Pharmaceutics, and Oral Biology

Alzheimer's Research Center

E-MAIL: alzheimr@umn.edu


Research Interests:

Dr. William H. Frey II is the Founder and Co-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.


Dr. Frey's non-invasive intranasal method for bypassing the blood-brain barrier to rapidly delivery and target therapeutic agents to the brain along the olfactory and trigeminal neural pathways while reducing systemic exposure and unwanted side effects has captured the interest of both pharmaceutical companies and neuroscientists.  The intranasal insulin treatment he developed for Alzheimer’s disease has been shown in multiple clinical trials to improve memory in both Alzheimer’s patients and normal adults. The intranasal therapeutic (stem) cell treatment he discovered has been shown to bypass the blood-brain barrier to treat Parkinson's, stroke, neonatal ischemia, multiple sclerosis and subarachnoid hemorrhage in animal models of these disorders.


Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

  • Fine JM, Forsberg AC, Stroebel BM, Faltesek KA, Verden DR, Hamel KA, Raney EB, Crow JM, Haase LR, Knutzen KE, Kaczmarczek KD, Frey WH, Hanson LR.Intranasal deferoxamine affects memory loss, oxidation, and the insulin pathway in the streptozotocin rat model of Alzheimer's disease. J Neurol Sci. 2017;380:164-171.
  • Belur LR, Temme A, Podetz-Pedersen K, Riedl M, Vulchanova L, Robinson N, Hanson LR, Kozarsky K, Orchard P, Frey WH 2nd, Low WC, McIvor RS. Intranasal adeno-associated virus mediated gene delivery and expression of human iduronidase in the central nervous system: A noninvasive and effective approach for prevention of neurologic disease in mucopolysaccharidosis type I. Hum Gene Ther. 2017;28:576-587.
  • Tzabazis A, Mechanic J, Miller J, Klukinov M, Pascual C, Manering N, Carson DS, Jacobs A, Qiao Y, Cuellar J, Frey WH 2nd, Jacobs D, Angst M, Yeomans DC. Oxytocin receptor: Expression in the trigeminal nociceptive system and potential role in the treatment of headache disorders. Cephalalgia. 2016;36:943-50.
  • Dhuria SV, Fine JM, Bingham D, Svitak AL, Burns RB, Baillargeon AM, Panter SS, Kazi AN, Frey WH 2nd, Hanson LR. Food consumption and activity levels increase in rats following intranasal Hypocretin-1. Neurosci Lett. 2016;627:155-9.
  • Krishnan JKS, Arun P, Appu AP, Vijayakumar N, Figueiredo TH, Braga MFM, Baskota S, Olsen CH, Farkas N, Dagata J, Frey WH 2nd, Moffett JR, Namboodiri AMA. ntranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning. Neurotoxicology. 2016;53:64-73
  • Fine JM, Renner DB, Forsberg AC, Cameron RA, Galick BT, Le C, Conway PM, Stroebel BM, Frey WH 2nd, Hanson LR. Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation. Neurosci Lett. 2015;584:362-367.
  • Danielyan L, Beer-Hammer S, Stolzing A, Schäfer R, Siegel G, Fabian C, Kahle P, Biedermann T, Lourhmati A, Buadze M, Novakovic A, Proksch B, Gleiter CH, Frey WH 2nd, Schwab M. Intranasal delivery of bone marrow derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease. Cell Transplant. 2014;23 Suppl 1:S123-39
  • Fine JM, Forsberg AC, Renner DB, Faltesek KA, Mohan KG, Wong JC, Arneson LC, Crow JM, Frey WH 2nd, Hanson LR. Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat model of Parkinson׳s disease.Brain Res. 2014;1574:96-104
  • Fine JM, Renner DB, Forsberg AC, Cameron RA, Galick BT, Le C, Conway PM, Stroebel BM, Frey WH 2nd, Hanson LR.. Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation. Neurosci. Lett. 2014;584:362-367
  • Rosenbloom MH, Barclay TR, Pyle M, Owens BL, Cagan AB, Anderson CP, Frey WH 2nd, Hanson LR. A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimer's disease.CNS Drugs 2014;28:1185–1189.
  • Freiherr J, Hallschmid M, Frey WH 2nd, Brünner YF, Chapman CD, Hölscher C, Craft S, De Felice FG, Benedict C. Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence. CNS Drugs 2013;27:505-514
  • William H. Frey II. Intranasal insulin to treat and protect against posttraumatic stress disorder. J Nerv Ment Dis. 2013;201:638-639.
  • Chapman CD, Frey WH II, Craft S, Danielyan L, Hallschmid M, Schioth HB, Benedict C. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res. 2013;30:2475-84.
  • Wolf DA, Hanson LR, Aronovich EL, Nan Z, Low WC, Frey WH 2nd, McIvor RS. Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration. Mol Genet Metab. 2012;106:131-134.
  • Fine JM, Baillargeon AM, Renner DB, Hoerster NS, Tokarev J, Colton S, Pelleg A, Andrews A, Sparley KA, Krogh KM, Frey WH, Hanson LR. Intranasal deferoxamine improves performance in radial arm water maze, stabilizes HIF-1α, and phosphorylates GSK3β in P301L tau transgenic mice. Exp Brain Res. 2012;219:381-390.
  • Hanson LR, Fine JM, Renner DB, Svitak AL, Burns RB, Nguyen TM, Tuttle NJ, Marti DL, Panter SS, Frey WH 2nd. Intranasal delivery of deferoxamine reduces spatial memory loss in APP/PS1 mice. Drug Deliv Transl Res. 2012;2:160-168
  • Renner DB, Frey WH 2nd, Hanson LR. Intranasal delivery of siRNA to the olfactory bulbs of mice via the olfactory nerve pathway. Neurosci Lett. 2012;513(2):193-197
  • Renner DB, Svitak AL, Gallus NJ, Ericson ME, Frey WH 2nd, Hanson LR. Intranasal delivery of insulin via the olfactory nerve pathway. J Pharm Pharmacol. 2012;64:1709-14.
  • Hanson LR, Fine JM, Hoekman JD, Nguyen TM, Burns RB, Martinez PM, Pohl J, Frey WH 2nd. Intranasal delivery of growth differentiation factor 5 to the central nervous system. Drug Deliv. 2012;19:149-54.
  • Schiöth HB, Frey WH, Brooks SJ, Benedict C. Insulin to treat Alzheimer's disease: just follow your nose? Expert Rev Clin Pharmacol. 2012;5:17-20.
  • Liu Z, Li Y, Zhang L, Xin H, Cui Y, Hanson LR, Frey WH 2nd, Chopp M. Subacute intranasal administration of tissue plasminogen activator increases functional recovery and axonal remodeling after stroke in rats. Neurobiol Dis. 2012;45:804-809.
  • Gomez D, Martinez JA, Hanson LR, Frey WH 2nd, Toth CC. Intranasal Treatment of Neurodegenerative Diseases and Stroke.Front Biosci (Schol Ed). 2012;4:74-89.
  • Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Bernhard F, Verleysdonk S, Buadze M, Lourhmati A, Klopfer T, Schaumann F, Schmid B, Koehle C, Proksch B, Weissert R, Reichardt HM, van den Brandt J, Buniatian GH, Schwab M, Gleiter CH, Frey WH 2nd. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson’s disease. Rejuvenation Res. 2011;14:3-16.
  • Francis GJ, Martinez JA, Liu WQ, Zochodne DW, Hanson LR, Frey WH 2nd, Toth C.. Motor endplate innervation loss in diabetes and the role of insulin. J Neuropathol Exp Neurol. 2011;70:323-339.
  • Benedict C, Frey WH 2nd, Schiöth HB, Schultes B, Born J, Hallschmid M. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments. Exp Gerontol. 2011;46(2-3):112-115
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