William H. Frey II, Ph.D.

Professor, Department of Neurology, Pharmaceutics, and Oral Biology

Alzheimer's Research Center

E-MAIL: [email protected]

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.)

  • Haass-Koffler CL, Kashyap B, Gully BJ, Nambiar SS, Hornbacher R, Foster SL, Silberman Y, Swift RM, Hanson LR, Frey WH 2nd. Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial. Contemp Clin Trials Commun. 2025 Jun 10;46:101509. 
  • Fine JM, Kosyakovsky J, Bowe TT, Faltesek KA, Stroebel BM, Abrahante JE, Kelly MR, Thompson EA, Westby CM, Robertson KM, Frey WH 2nd, Hanson LR. Low-dose intranasal deferoxamine modulates memory, neuroinflammation, and the neuronal transcriptome in the streptozotocin rodent model of Alzheimer's disease. Front Neurosci. 2025 Jan 13;18:1528374. 
  • Rao IY, Hanson LR, Johnson JC, Rosenbloom MH, Frey WH 2nd. Brain glucose hypometabolism and iron accumulation in different brain regions in Alzheimer's and Parkinson's Diseases. Pharmaceuticals (Basel). 2022 Apr 29;15(5):551. 
  • Belur LR, Romero M, Lee J, Podetz-Pedersen KM, Nan Z, Riedl MS, Vulchanova L, Kitto KF, Fairbanks CA, Kozarsky KF, Orchard PJ, Frey WH 2nd, Low WC, McIvor RS. Comparative effectiveness of intracerebroventricular, intrathecal, and intranasal routes of AAV9 vector administration for genetic therapy of neurologic disease in murine mucopolysaccharidosis Type I. Front Mol Neurosci. 2021 May 10;14:618360.
  • Grijota-Martínez C, Bárez-López S, Ausó E, Refetoff S, Frey WH 2nd, Guadaño-Ferraz A. Intranasal delivery of Thyroid hormones in MCT8 deficiency. PLoS One. 2020 Jul 20;15(7):e0236113.
  • Kosyakovsky J, Witthuhn BA, Svitak AL, Frey WH 2nd, Hanson LR, Fine JM. Quantifying intranasally administered deferoxamine in rat brain tissue with mass spectrometry. ACS Chem Neurosci. 2019 Nov 20;10(11):4571-4578.
  • 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.
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