William H. Frey II, PhD, is a Senior Research Investigator and former Senior Director of Neuroscience Research at the HealthPartners Center for Memory and Aging. Dr. Frey completed his undergraduate training in Chemistry at Washington University in St. Louis, followed by a PhD in Biochemistry at Case Western Reserve University and postdoctoral training in Pharmacology at the University of Minnesota. A pioneering neuroscientist with decades of contributions to neurodegenerative disease research, Dr. Frey is internationally recognized for inventing the intranasal delivery method that enables therapeutics to bypass the blood–brain barrier — a discovery that has shaped modern approaches to Alzheimer’s disease and CNS drug delivery. He has led groundbreaking research on intranasal insulin, intranasal stem cells, and numerous neuroprotective agents, and his work has been highlighted by major national and international media outlets.

Dr. Frey has developed patented treatments targeting noninvasive delivery of therapeutic agents to the brain and spinal cord for neurological, psychiatric, and metabolic disorders. He has co‑authored clinical and preclinical studies demonstrating the effectiveness of intranasal insulin for Alzheimer’s disease, traumatic brain injury, Down syndrome, Parkinson’s disease, and diabetic neuropathy. Across a research career spanning more than four decades, Dr. Frey has published extensively and has directed numerous research programs, laboratories, and collaborative initiatives focused on advancing translational neuroscience.

Research interests

Pioneering intranasal therapeutic delivery to the brain and spinal cord. Dr. Frey is best known for inventing the intranasal administration method that enables peptides, proteins, stem cells, and other therapeutic agents to reach the brain and spinal cord while bypassing the blood–brain barrier (U.S. Patent 5,624,898). His research established intranasal insulin as a treatment for Alzheimer’s disease (U.S. Patent 6,313,093) and contributed foundational work on intranasal deferoxamine, growth factors, and mesenchymal stem cells for neurodegenerative disease. These discoveries laid the framework for numerous current translational programs worldwide.

Advancing Alzheimer’s disease and neurodegeneration therapeutics. Dr. Frey has led or contributed to decades of research on Alzheimer’s disease, including intranasal insulin, intranasal deferoxamine, nerve growth factor transport, anti‑inflammatory approaches, oxidative stress mechanisms, amyloid biology, iron metabolism, and neurochemical changes in AD. He has served as principal or co‑investigator on multiple NIH, VA, state, foundation, and industry‑funded studies, spanning mechanistic research, pharmacokinetics, gene expression changes, animal models, and early translational work.

Developing therapies for traumatic brain injury and stroke. Dr. Frey’s research includes multiple programs developing intranasal insulin, deferoxamine, growth factors, and neuroprotective agents for traumatic brain injury, concussion, ischemic stroke, and subarachnoid hemorrhage. His studies have demonstrated improved motor function, reduced infarct volume, enhanced neurogenesis, and favorable molecular response profiles across several preclinical models. He is an inventor on patents for treating TBI and ischemic injury via intranasal delivery.

Stem cell and gene‑based intranasal therapies. Dr. Frey has co‑led pioneering work showing that mesenchymal stem cells, macrophages, microglia, and genetically engineered cells can be delivered intranasally to target the CNS in models of Alzheimer’s disease, Parkinson’s disease, and glioma. He has also contributed to intranasal AAV gene‑delivery approaches for lysosomal storage diseases and other neurologic conditions.

Psychiatric, metabolic, and pain‑related applications of intranasal therapeutics. Dr. Frey’s research and patents extend intranasal delivery to PTSD, addiction, seizure disorders, social communication disorder, anorexia nervosa, migraine and headache syndromes (via oxytocin and related mechanisms), diabetic neuropathy, and metabolic dysregulation.

Conducting Institute research since: 1977

Current research activities and funding

• Co-Investigator – Therapeutic Strategy to Treat Alzheimer’s Disease by VGF Delivery into Brain (NIA, 2023-2028)
• Co‑Investigator — Translation of Intranasal Insulin for the Treatment of Traumatic Brain Injury (Department of Defense, 2022-2026)
• Co-Investigator – Intranasal Insulin for the treatment of Spinal Cord Injury, Phase I (Department of Defense, 2023-2026)
• Co-Investigator – Intranasal insulin for the treatment of mild Traumatic Brain Injury, Phase II (Regions Hospital Foundation, 2026-2029)
• Co-Investigator – Intranasal insulin for the treatment of alcohol use disorder, Phase II (NIAAA, 2024-2026)

Education and training

• B.A., Chemistry — Washington University, St. Louis, MO (1969)
• Ph.D., Biochemistry — Case Western Reserve University, Cleveland, OH (1975)
• Postdoctoral Training, Pharmacology — University of Minnesota, Minneapolis, MN (1977) 

Affiliations, appointments, and honors

Selected positions and appointments

• Senior Research Director of Neuroscience Research, HealthPartners Center for Memory and Aging (1997–2025)
• Professor, Department of Pharmaceutics, University of Minnesota (1997–2016)
• Professor, Department of Oral Biology, University of Minnesota (2006–2014)
• Visiting Professor, SF VA Medical Center (2002–2015)
• Research Director, Alzheimer’s Research Center, Regions Hospital (1985–1997)
• Director, Psychiatry Research Laboratories, St. Paul–Ramsey Medical Center (1980–1991)
• Assistant Professor, Departments of Neurology, Psychiatry, and Neuroscience, University of Minnesota (1977–1984)
• Former Editor, Journal of Alzheimer’s Disease (1997–2000)
• Member, Minnesota Governor’s Task Force on Alzheimer’s Disease (1988–1992)
• Organizer and Co‑Chair, Fourth International Conference on Alzheimer’s Disease and Related Disorders (1992–1994)

Honors

• Multiple U.S. and international patents for intranasal drug and stem cell delivery technologies (1997–present)