Frey II, William H., PhD
Sr. Director of Neuroscience Research, Center for Memory & Aging
About

Overview/research interests: Intranasal delivery of therapeutics to treat and prevent brain damage from Alzheimer’s disease, Parkinson’s disease, stroke, traumatic brain injury, posttraumatic stress disorder, brain tumors and other brain disorders.

  • Developed noninvasive, intranasal method for bypassing the blood-brain barrier to target central nervous system therapeutic agents to the brain and spinal cord while reducing system exposure and unwanted side effects
  • Developed and patented intranasal insulin and showed that intranasal insulin improves memory in patients with Alzheimer’s disease
  • Developed and patented method using intranasal insulin to treat and protect against traumatic brain injury
  • Developed method using intranasal insulin to treat and protect against posttraumatic stress disorder
  • Developed and patented intranasal deferoxamine for the treatment of Alzheimer’s disease, stroke, Parkinson’s disease, traumatic brain injury and other central nervous system disorders
  • Developed and patented intranasal stem cells to bypass the blood-brain barrier and treat Parkinson’s disease, stroke, Alzheimer’s disease and other central nervous system disorders
  • Leading expert in why humans uniquely evolved the ability to shed emotional tears in response to stress and the chemistry of emotional tears
  • Research has been subject of articles in the New York Times, Wall Street Journal, U.S. News and World Report and numerous other newspapers and magazines
  • Interviewed on the Today Show, Good Morning America, 20/20, All Things Considered, the BBC and numerous other TV and radio programs around the world

Current research activities and funding: Intranasal delivery of therapeutics to treat and prevent brain damage from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, traumatic brain injury, posttraumatic stress syndrome and other central nervous system disorders.

Overview
geographic focus
  • Minnesota  State or Province
  • Affiliation
    positions
  • Sr. Director, Neuroscience Research Centers 1977 -
  • has collaborator
  • Hanson, Leah R., PhD  Senior Director, Neuroscience Research, and Senior Investigator, HealthPartners Institute
  • Publications
    selected publications
    Journal Article
  • A non-invasive direct nose to brain drug delivery platform vs. invasive brain delivery approach: patient-centered care impact analysis
    Drug delivery. 2022
  • A phase II, single-center, randomized, double-blind, placebo-controlled study of the safety and therapeutic efficacy of intranasal glulisine in amnestic mild cognitive impairment and probable mild Alzheimer's disease
    Drugs and Aging. 2021
  • Comparative effectiveness of intracerebroventricular, intrathecal, and intranasal routes of AAV9 vector administration for genetic therapy of neurologic disease in murine mucopolysaccharidosis type I
    Frontiers in Molecular Neuroscience. 2021
  • Losartan improves memory, neurogenesis and cell motility in transgenic Alzheimer's mice
    Pharmaceuticals (Basel, Switzerland). 2021
  • Nasal oxytocin for the treatment of psychiatric disorders and pain: achieving meaningful brain concentrations
    Translational psychiatry. 2021
  • Antifibrotic effects of amyloid-beta and Its loss in cirrhotic liver
    Cells. 2020
  • Cell motility and migration as determinants of stem cell efficacy
    EBioMedicine. 2020
  • Double-blind placebo-controlled pilot investigation of the safety of a single dose of rapid-acting intranasal insulin in Down syndrome
    Drugs in R&D. 2020
  • Intranasal deferoxamine can improve memory in healthy C57 mice, suggesting a partially non-disease-specific pathway of functional neurologic improvement
    Brain and behavior. 2020
  • Intranasal delivery of low-dose insulin ameliorates motor dysfunction and dopaminergic cell death in a 6-OHDA rat model of Parkinson's Disease
    Neuroscience Letters. 2020
  • Intranasal delivery of thyroid hormones in MCT8 deficiency
    PloS One. 2020
  • Intranasal losartan decreases perivascular beta amyloid, inflammation, and the decline of neurogenesis in hypertensive rats
    Neurotherapeutics. 2019
  • Quantifying intranasally administered deferoxamine in rat brain tissue with mass spectrometry
    ACS Chemical Neuroscience. 2019
  • Pharmacokinetics in rat of P8, a peptide drug candidate for the treatment of Alzheimer's disease: stability and delivery to the brain
    Journal of Alzheimer's disease reports. 2018
  • 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
    Human Gene Therapy. 2017
  • Intranasal deferoxamine affects memory loss, oxidation, and the insulin pathway in the streptozotocin rat model of Alzheimer's disease
    Journal of the Neurological Sciences. 2017
  • Intranasal insulin treatment of an experimental model of moderate traumatic brain injury
    Journal of Cerebral Blood Flow and Metabolism. 2017
  • Food consumption and activity levels increase in rats following intranasal Hypocretin-1
    Neuroscience Letters. 2016
  • Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning
    Neurotoxicology. 2016
  • Intranasal drug delivery bypasses the blood–brain barrier
    2016
  • Oxytocin receptor: expression in the trigeminal nociceptive system and potential role in the treatment of headache disorders
    Cephalalgia. 2016
  • Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation
    Neuroscience Letters. 2015
  • Intranasal delivery of therapeutic neural stem cells to target intracerebral glioma
    2015
  • Noninvasive intranasal stem cells bypass the blood-brain barrier to target the brain to treat Parkinson's disease, stroke, MS, brain tumors, cerebral ischemia, Alzheimer's and other CNS disorders
    2015
  • . 2008;157:908-25]
    Neuroscience. 2014
  • . 2012 Jan 11;8:3]
    Molecular Pain. 2014
  • A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein e4 carriers with mild-moderate Alzheimer's disease
    2014
  • 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 Transplantation. 2014
  • Intranasal delivery, a quick and effective way to deliver therapeutics to the brain
    AAPS (American Association of Pharmaceutical Scientists) Newsmagazine. 2014
  • Intranasal insulin: a potential therapeutic for post-traumatic stress disorder and Alzheimer's
    Minn Physician. 2014
  • Intranasally-administered deferoxamine mitigates toxicity of 6-OHDA in a rat model of Parkinsons disease
    Brain Research. 2014
  • Post-traumatic stress disorder: new approach may help prevent, as well as treat, this devastating disorder
    2014
  • Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states:
    Molecular Pain. 2012
  • Intranasal deferoxamine improves performance in radial arm water maze, stabilizes HIF-1alpha, and phosphorylates GSK3beta in P301L tau transgenic mice
    Experimental Brain Research. 2012
  • Intranasal delivery of deferoxamine reduces spatial memory loss in APP/PS1 mice
    Drug delivery and translational research. 2012
  • Intranasal delivery of growth differentiation factor 5 to the central nervous system
    Drug delivery. 2012
  • Intranasal delivery of insulin via the olfactory nerve pathway
    Journal of Pharmacy and Pharmacology. 2012
  • Intranasal delivery of siRNA to the olfactory bulbs of mice via the olfactory nerve pathway
    Neuroscience Letters. 2012
  • Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration
    Molecular Genetics and Metabolism. 2012
  • Special delivery: intranasal treatments bypass blood-brain barrier to treat Alzheimer's and other brain disorders
    Minn Physician. 2012
  • Subacute intranasal administration of tissue plasminogen activator increases functional recovery and axonal remodeling after stroke in rats
    Neurobiology of Disease. 2012
  • Intranasal delivery of CNS therapeutics
    AAPS (American Association of Pharmaceutical Scientists) Newsmagazine. 2011
  • Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke
    Journal of Neuroscience. 2011
  • Intranasal phosphoramidon increases beta-amyloid levels in wild-type and NEP/NEP2-deficient mice
    Journal of Molecular Neuroscience. 2011
  • Motor end plate innervation loss in diabetes and the role of insulin
    Journal of Neuropathology and Experimental Neurology. 2011
  • Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease
    Rejuvenation research. 2011
  • Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain
    Molecular Pain. 2010
  • Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS
    Journal of Drug Targeting. 2010
  • Protective effects of intranasal losartan in the APP/PS1 transgenic mouse model of Alzheimer disease
    Rejuvenation research. 2010
  • Trigeminal pathways deliver a low molecular weight drug from the nose to the brain and orofacial structures
    Molecular Pharmaceutics. 2010
  • Human and rodent amyloid-beta peptides differentially bind heme: relevance to the human susceptibility to Alzheimer's disease
    Archives of Biochemistry and Biophysics. 2009
  • Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke
    Journal of Pharmacology and Experimental Therapeutics. 2009
  • Intranasal drug targeting of hypocretin-1 (orexin-A) to the central nervous system
    Journal of Pharmaceutical Sciences. 2009
  • Novel vasoconstrictor formulation to enhance intranasal targeting of neuropeptide therapeutics to the central nervous system
    Journal of Pharmacology and Experimental Therapeutics. 2009
  • Delivery of interferon-beta to the monkey nervous system following intranasal administration
    Neuroscience. 2008
  • Intranasal administration delivers peptoids to the rat central nervous system
    Neuroscience Letters. 2008
  • Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone
    BMC Neuroscience. 2008
  • Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults
    Journal of Alzheimer's Disease. 2008
  • New therapeutic approach for brain tumors: Intranasal delivery of telomerase inhibitor GRN163
    Neuro-Oncology. 2008
  • Inhibition of ligand binding to G protein-coupled receptors by arachidonic acid
    Journal of Molecular Neuroscience. 2005
  • Intranasal administration of interferon beta bypasses the blood-brain barrier to target the central nervous system and cervical lymph nodes: a non-invasive treatment strategy for multiple sclerosis
    Journal of Neuroimmunology. 2004
  • The window of opportunity for treatment of focal cerebral ischemic damage with noninvasive intranasal insulin-like growth factor-I in rats
    Journal of Stroke and Cerebrovascular Diseases. 2004
  • Inactivation of the human brain muscarinic acetylcholine receptor by oxidative damage catalyzed by a low molecular weight endogenous inhibitor from Alzheimer's brain is prevented by pyrophosphate analogs, bioflavonoids and other antioxidants
    Brain Research. 2002
  • Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusion
    Neuroscience Letters. 2001
  • Inconsistency between severe substantia nigra degeneration with Lewy bodies and clinical parkinsonism in dementia patients: a cliniconeuropathological study
    Acta Neuropathologica. 2000
  • Pure hippocampal sclerosis: a rare cause of dementia mimicking Alzheimer's disease
    Neurology. 2000
  • Endogenous Alzheimer's brain factor and oxidized glutathione inhibit antagonist binding to the muscarinic receptor
    Brain Research. 1996
  • Quantitative analysis of the olfactory pathway for drug delivery to the brain
    Brain Research. 1995
  • Clinical characteristics of chronic Creutzfeldt-Jakob disease
    Journal of Geriatric Psychiatry and Neurology. 1994
  • Free D-amino acids in human cerebrospinal fluid of Alzheimer disease, multiple sclerosis, and healthy control subjects
    Molecular and Chemical Neuropathology. 1994
  • Inhibitor of antagonist binding to the muscarinic receptor is elevated in Alzheimer's brain
    Brain Research. 1994
  • Seizures in Alzheimer's disease: clinicopathologic study
    Journal of Geriatric Psychiatry and Neurology. 1994
  • Serum cytokine levels in patients with Alzheimer's disease
    Clinical and Diagnostic Laboratory Immunology. 1994
  • Transforming growth factor beta in Alzheimer's disease
    Clinical and Diagnostic Laboratory Immunology. 1994
  • Two cases of acute anti-GM1 antibody elevations in response to exogenous GM1 without neurological symptoms
    Journal of Neuroimmunology. 1994
  • Pick's disease versus Alzheimer's disease: a comparison of clinical characteristics
    Neurology. 1993
  • Silica-ELISA method improves detection and quantitation of minor glycolipid components in lipid mixtures and of other antigens
    Journal of Immunological Methods. 1993
  • A clinicopathological study of CT scans in Alzheimer's disease
    Journal of the American Geriatrics Society. 1992
  • Altered aspartate in Alzheimer neurofibrillary tangles
    Neurochemical Research. 1992
  • Clinically diagnosed Alzheimer disease: neuropathologic findings in 650 cases
    Alzheimer Disease and Associated Disorders. 1992
  • Deletion in the prion protein gene in a demented patient
    Human Molecular Genetics. 1992
  • Multiple sclerosis dementia
    Neurology. 1992
  • Racemized D-aspartate in Alzheimer neurofibrillary tangles
    Brain Research Bulletin. 1992
  • Risk factors in Alzheimer's disease: a clinicopathologic study
    Neurology. 1992
  • Neuropathologically confirmed Alzheimer's disease: clinical diagnoses in 394 cases
    Journal of Geriatric Psychiatry and Neurology. 1991
  • Seasonal distribution of births in Alzheimer's disease
    International Psychogeriatrics. 1991
  • Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia
    Neurology. 1990
  • GM-1 treatment of Alzheimer's disease. A pilot study of safety and efficacy
    Archives of Neurology. 1990
  • Immunogold labeling of Alzheimer paired helical filaments with ganglioside MAB A2B5
    Alzheimer Disease and Associated Disorders. 1990
  • D-aspartate in human brain
    Journal of Neurochemistry. 1987
  • Ganglioside monoclonal antibody (A2B5) labels Alzheimer's neurofibrillary tangles
    Neurology. 1987
  • Glial fibrillary acidic protein and Alzheimer's disease
    Neurochemical Research. 1985
  • Human brain tubulin purification: decrease in soluble tubulin with age
    Neurochemical Research. 1985
  • A comparison of peripheral and central human muscarinic cholinergic receptor affinities for psychotropic drugs
    Biological Psychiatry. 1982
  • Postmortem stability of dopamine-sensitive adenylate cyclase, guanylate cyclase, ATPase, and GTPase in rat striatum
    Journal of Neurochemistry. 1981
  • Stimulation of guanylate cyclase by EDTA and other chelating agents
    Biochimica et Biophysica Acta. 1981
  • Effect of dopamine on activation of rat striatal adenylate cyclase by free Mg2+ and guanyl nucleotides
    Journal of Neurochemistry. 1980
  • Review
  • Brain glucose hypometabolism and iron accumulation in different brain regions in Alzheimer's and Parkinson's diseases [review]
    Pharmaceuticals (Basel, Switzerland). 2022
  • Mechanisms of intranasal deferoxamine in neurodegenerative and neurovascular disease [review]
    Pharmaceuticals (Basel, Switzerland). 2021
  • Intranasal insulin: a treatment strategy for addiction [review]
    Neurotherapeutics. 2020
  • Oxytocin and migraine headache [review]
    Headache. 2017
  • Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence [review]
    2013
  • Intranasal insulin to treat and protect against posttraumatic stress disorder [review]
    Journal of Nervous and Mental Disease. 2013
  • Intranasal treatment of central nervous system dysfunction in humans [review]
    Pharmaceutical Research. 2013
  • Brain insulin signaling and Alzheimer's disease: current evidence and future directions [review]
    Molecular Neurobiology. 2012
  • Intranasal treatment of neurodegenerative diseases and stroke [review]
    Frontiers in bioscience (Scholar edition). 2012
  • Intranasal insulin as a therapeutic option in the treatment of cognitive impairments [review]
    Experimental Gerontology. 2011
  • Intranasal delivery to the central nervous system: mechanisms and experimental considerations [review]
    Journal of Pharmaceutical Sciences. 2010
  • Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease [review]
    BMC Neuroscience. 2008
  • Strategies for intranasal delivery of therapeutics for the prevention and treatment of neuroAIDS [review]
    Journal of Neuroimmune Pharmacology. 2007
  • presentations
    Presentation
  • Alzheimer's research preview [presentation]
  • Beyond the basics of Alzheimer's; new treatments, approaches and research: intranasal insulin, drugs and adult stem cells by pass the blood-brain barrier to treat Alzheimer's, Parkinson's and other brain disorders [presentation]
  • Beyond the basics of Alzheimer's; new treatments, approaches and research: intranasal insulin, drugs and adult stem cells by pass the blood-brain barrier to treat Alzheimer's, Parkinson's and other brain disorders [presentation]
  • Beyond the basics of Alzheimer's; new treatments, approaches and research: intranasal insulin, drugs and adult stem cells by pass the blood-brain barrier to treat Alzheimer's, Parkinson's and other brain disorders [presentation]
  • Current research [presentation]
  • Diet is not just about calories: Let's think differently about diet, the brain and memory loss [presentation]
  • Intranasal deferoxamine improves spatial memory through a non-amyloid mechanism in APP/PS1 mice [presentation]
  • Intranasal deferoxamine prevents memory loss in the intracerebroventricular streptozotocin rat [presentation], International Conference on Alzheimer's Disease Annual Meeting
  • Intranasal insulin, drugs and stem cells bypass the blood-brain barrier to treat Alzheimer's, Parkinson's and other brain disorders [presentation]
  • New treatment options for Alzheimer's, Parkinson's and other brain disorders [presentation]
  • New treatment options for Alzheimer's, Parkinson's and other brain disorders [presentation]
  • Proteomic approach to the study of neuroprotection following intranasal deferoxamine [presentation]
  • Targeting to the brain: the nose knows [presentation]
  • Contact
    primary email
  • William.H.Frey@healthpartners.com
  • located in facility

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