Walter C. Low, PhD

Dr. Low’s research is focused on translating neuroscience developments from the laboratory to the clinic. He has been involved in a number of technologies that include neural progenitor/stem cell therapies, gene therapies, neuroprotective therapies, and medical devices for treating a variety of neurological conditions. Neural disorders of interest include ischemic and hemorrhagic stroke, Parkinson’s disease, brain tumors, Alzheimer’s disease, lysosomal storage disorders of the brain, Huntington’s disease, spinal cord injury, and traumatic brain injury.

Dr. Low’s group was the first to:

• Demonstrate that the transplantation of cholinergic neurons into the hippocampal formation could restore learning and memory function in a rat model of Alzheimer’s disease
• Demonstrate the efficacy of immunotherapy for eradicating intracranial tumors in rodents
• Receive FDA approval for clinical trials in the United States to study the efficacy of deep brain stimulation for the treatment of Parkinson’s disease.

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Brain and tumor immunology and development of cancer vaccines

Dr. Low’s laboratory is focused on the study of brain tumors. Primary tumors that originate in the brain represent some of the most malignant types of cancers. Patients diagnosed with grade IV glioblastoma multiforme have a mean survival time of 11 months after diagnosis. Our studies of brain tumors have emphasized the development of immunotherapeutic approaches for the treatment of these tumors. Cancer vaccines consisting of cytokines and tumor antigens are used to stimulate cells of the immune system to recognize and destroy tumors within the brain.

• 2018-2019 (PI) National Institutes of Health, MN-REACH: “Treatment of Malignant Brain Tumors with the Zika Virus as a Vaccine Adjuvant and Oncolytic Virus” U01 HL127479
• 2018-2020 (Co-Investigator) Regenerative Medicine Minnesota, “Neuroprotection Using Human Extremely Low Gestational Age Neonate-Derived Umbilical Cord Blood Stem Cells in Neonatal Hemorrhagic Brain Injury”
• 2017-2020 (Co-Investigator) National Institutes of Health, “High Density Multi-electrode Arrays with Spatially Selective Unidirectional and Rotating Fields for Investigation of Neural Networks” U01 NS103569
• 2017-2019 (PI) Regenerative Medicine Minnesota, “Production of Dopamine Neurons – A Cellular Product for Treating Parkinson’s Disease”
• 2017-2019 (Co-Investigator) National Institutes of Health, MN-REACH Program: “Midbrain Organoid-Derived Product for Treatment of Parkinson’s Disease” U01 HL127479
• 2017-2018 (PI) Randy Shaver Cancer Research Foundation, “Harnessing the Zika Virus to Target Malignant Brain Tumors”
• 2016-2018 (Co-Investigator) Regenerative Medicine Minnesota, “Generating Human Neural Stem Cells and Progenitor Cells in a Porcine Model Through Blastocyst Complementation”
• 2016-2018 (Co-Principal Investigator) Academic Health Center, University of Minnesota, “Generating Human Pancreas in Gene Edited Pigs”
• 2016-2018 (Co-Investigator) Minnesota Partnership Infrastructure Fund, State of Minnesota, “3-Dimensional Nanoscale Resolution Microscope for Understanding Human Disease Processes” 
• 2016-2018 (Co-Investigator) Grant-in-Aid program, University of Minnesota, “Modulating Macrophages to Enhance Neurogenesis in Alzheimer Disease”
• 2016-2017 (Co-Investigator) Institute for Engineering in Medicine, University of Minnesota, “Generating Exogenic Human Liver and Hepatocytes”
• 2015-2018 (Co-Investigator) Department of Defense, “Exogenic Human Heart in Gene-Edited Animals”

• “GM-CSF Administration for the Treatment and Prevention of Recurrence of Brain Tumors,” U.S. Patent No. 5,837,231 (1995)
• “Antisense Oligonucleotides and Methods for Treating Central Nervous System Tumors," U.S. Patent No. 5,994,320 (1996)
• “Insulin-like Growth Factor 1 Receptor (IGF-1R) Antisense Oligonucleotide-Based Vaccine for the Treatment of Breast Tumors,” U.S. Patent No.6,071,891 (1996)
• “Methods of Use of Beta1-Integrin Inhibitors”, University of Minnesota, Office of Patents and Technology Marketing, PCT/US00/07680 (2001) - Abandoned by UMN
• “Methods of Use of B1-Integrin Inhibitors”, University of Minnesota, Office of Patents and Technology Marketing, UM Docket No. Z00080, U.S. Patent Application Serial No. 09/937,076 (2002) - Abandoned by UMN
• “Methods of Treating Injuries of the Nervous System Associated with Hemorrhage, ”University of Minnesota, Office of Patents and Technology Marketing, UM Docket No. Z03027, U.S. Patent Application Serial No. 60/451,615 (2003)
  European Patent EP1575578 (A2) (Granted 2009)
  China Patent ZL200380102834.4 (03826252.5) (Granted 2009)
  Hong Kong Patent 1086479A (Granted 2009)
  France 1575578 (Granted 2009)
  Germany 60330501.6-08 (Granted 2009)
  United Kingdom 1575578 (Granted 2009)
  U.S. Patent US2006-0135494 (pending 2010)
  Vietnam Patent 1-2005-00758 (pending 2010)
• “Methods of Promoting Cell Viability”, University of Minnesota, Office of Patents and Technology Marketing, Docket No. Z03028 - 110.01990101 (2003)
  U.S. Patent 2006/0204481 (pending 2010)
  European Patent 03723869.7 (EP1615497) (Granted 2010)
  Japan Patent 2004-571396 (pending 2010)
  Vietnam Patent 1-2005-01607 (pending 2010)
• “Protection Against Nervous System Toxins”, Invention Disclosure, University of Minnesota, Office of Patents and Technology Marketing (2003)
• “Use of Human Umbilical Cord Stem Cells to Treat Ischemic Event”, University of Minnesota, Office of Patents and Technology Marketing, UM Docket 600.623PV (2004), U.S. Patent No. 8,309,070 (2012)
• “Methods for Treating Vision Disorders”, University of Minnesota, Office of Patents and Technology Marketing, M&R Docket No.: 110.02650160 (2005)
  European patent EP1871385 (Granted 2010)
  U.S. patent 20080194531 (A1) (pending 2010)
  Japan patent number JP 2008530100 (pending 2010)
• “Umbilical Cord Blood Stem Cells”, Patent License to Saneron CCEL, Tampa Bay, Florida, (2005)
• “Repair of Ischemic Heart Injury with Cord Blood Stem Cells”, UM Docket #Z06124 (2006).
• “CpGs for treating Brain Tumors”, UM Docket # (2007)
• “Mathematical Analyses of Magnetic Resonance Spectroscopy in the Diagnosis, Assessment of Clinical Change, and Metabolic Investigation of Disease” UM Docket # 1008-055USP1 (2009)
• “Vaccine Therapeutic Composition and Methods for Treating or Inhibiting Glioblastoma,” U.S. Patent Application Serial No.: 61/406,429 (2010)’ PCT/US2011/057654 (2011), U.S. Patent No. 9,364,505 B2 (June 14, 2016)
• “Ovarian Cancer Prognosis”, U.S. Patent Application Serial No.: 61/481,556 (2011)
• “Methods to Treat Mucopolysaccharide Type I or deficiencyin Alpha-L-Iduronidase using a Recombinant Adeno-Associated Virus Encoding Alpha-L-Iduronidase, University of Minnesota Docket No. 600.915PRV, Serial No. 61/823,757 (2013), U.S. Patent No. 9,827,295 (2017)
• “Magnetic Brain Array for Neuron Modulation and Mapping,” University of Minnesota Docket # 20150177 (2015)
• “Engineering of Humanized Dopamine Neurons by Genetic Complementation,” University of Minnesota and Recombinetics (2015) 
• “Deuterated Bile Acids”, U.S. Patent No. 9,708,362 (2017)
• “Methods and Compositions for Treating Glioma and Medulloblastoma Brain Tumors using the Zika Virus” (UMN Docket #920171.00171)

Publications
The following publications have received more than 15,967 citations in the scientific literature. Seventeen articles have received more than 100 citations. The h-index for the scientific impact of these publications is 54 and is ranked above the 95th percentile among faculty in academic neurosurgery departments in the United States. Here is a selection:

• Laoharawee K, Podetz-Pedersen K, Nguyen T, Fairbanks C, Low WC, Kozarsky K, and McIvor RS, Prevention of neurocognitive deficiency in mucopolysaccharidosis type II mice by CNS-directed AAV9-mediated sulfatase gene transfer, Human Gene Therapy, ePub ahead of print (2017)
• Belur LR, Temme A, Podetz-Pedersen KM, Riedl M, Vulchanova L, Robinson N, Hanson LR, Kozarsky K, Frey WH, Low WC, and McIvor RS, Intranasal AAV mediated gene delivery and expression of human iduronidase in the CNS: A non-invasive and effective approach for prevention of neurologic disease in mucopolysaccharidosis type I. Human Gene Therapy, ePub ahead of print (2017)
• Gardeck AM, Sheehan J, and Low WC, Immune and viral therapies for brain cancer. Expert Opinion on Biological Therapies 17:457-474 (2017)
• Lehto LJ, Slopsema JP, Johnson MD, Shatillo A, Teplitzky B, Utecht L, Adriany G, Mangia S, Sierra A, Low WC, Grohn O, and Machaeli S, Orientation selective deep brain stimulation, Journal of Neural Engineering, 14:016016 ePub ahead of print (2017)
• Parry GJ, Rodrigues CMP, Low WC, Hilbert SJ, and Steer CJ, Ursodeoxycholic acid may slow progression of amyotrophic later sclerosis. Annals of Neurodegenerative Disorders ePub ahead of print (2016).
• Stone LLH, Xiao F, Rotshafer J, Juliano M, Sanberg CD, Sanberg PR, Kuzmin-Nichol N, Grande A, Cheeran MC, and Low WC. Amelioration of ischemic brain injury in rats with human umbilical cord blood stem cells: Mechanisms of action, Cell Transplantation, 25:1473-1488 (2016).
• Terzic D, Maxon JR, Krevitt L, DiBartolomeo, Goyal T, Dutton JR, Low WC, and Parr AM, Directed differentiation of oligodendrocyte progenitor cells from mouse induced pluripotent stem cells, Cell Transplantation, 25:411-424 (2016).
• Satzer, D, Miller, C, Maxon J, Dibartolomeo C, Dutton JR, Low WC, and Parr AM, T cell deficiency in spinal cord injury – altered locomotor recovery and whole-genome transcriptional analysis, BMC Neuroscience16:74 Epub ahead of print (2015).
• Divani AA, Murphy AJ, Meints J, Sadeghi-Bzargani H, Nordberg J, Monga M, Low WC, Bhatia PM, Beilman GJ, and SantaCruz KS, A novel preclinical model of moderate primary blast-induced traumatic brain injury, Journal of Neurotrauma, 32:1109-1116 (2015).
• Satzer D, DiBartolomeao C, Ritchie MM, Storino C, Idiyatullin D, Mangia S, Michaeli S, Parr AM, and Low WC, Assessment of dysmyelination with RAFF MRI – application to murine MPS I, PLoS ONE 10:e0116788 (2015).

Books

• Low WC and CM Verfaillie, Editors, Stem Cells and Regenerative Medicine, World Science Press, Hakensack, NJ, (2008)
• Low, W.C., Analysis of Neurophysiological Plasticity within the Hippocampal Formation, University Microfilms, Xerox Corporation, Ann Arbor, Michigan (1979).

Chapters in Books (Selected)

• Stone LL, Low WC, and Grande A. Stem cell therapies for ischemic stroke, in Stem Cells in Neurogenerative Disease, Ed. by L Lescaudron, J Rossignol, and GL Dunbar, CRC Press, London, UK, pgs. 142-156, (2014).
• Keene CD, Ortiz-Gonzalez XR, Jiang Y, Verfaillie CM, and Low WC, Therapeutic application of bone marrow- derived stem cells in neuralgic injury and disease. In: Cell Therapies for Central Nervous System Disorders, Ed. by P.R. Sanberg, Humana Press (2005).
• Triarhou, L.C., W.C. Low, and B. Ghetti, Neurological mutant mice as models in neural transplantation, In: Intracerebral Transplantation, Ed. by Q.Y. Xu and S. S Jiao, The Science Press, Beijing, pp. 66-72 (2000).
• Low, W.C. and Y.J. Li, Neural transplantation of dopamine containing tissue into the striatum of animals with nigrostriatal dopamine deficits, In: Intracerebral Transplantation, Ed. by Q.Y. Xu and S. S Jiao, The Science Press, Beijing, pp. 78-85 (2000).
• Low, W.C. and Y.J. Li, Intrahippocampal grafts of cholinergic neurons: Survival, innervation, and functional restoration, In: Intracerebral Transplantation, Ed. by Q.Y. Xu and S. S Jiao, The Science Press, Beijing, pp. 108-113 (2000).

Posters (Selected)

• Toman N, Shaio ML, Voth J, Danczyk G, and Low WC, Assessing the ability of the Zika virus to infect human GBM6 and U87 gliomas, Peyton Society 80th Anniversary Meeting, Minneapolis, MN 2017
• Pearce CM, Shiao ML, and Low WC, Zika virus targeting of human DAOY medulloblastoma, Peyton Society 80th Anniversary Meeting, Minneapolis, MN 2017
• Sipe CJ, Shiao ML, and Low WC, Characterization of the Zika virus as an oncolytic virus in murine GL261 gliomas, Peyton Society 80th Anniversary Meeting, Minneapolis, MN 2017
• Voth J, Miller ZD, Danczyk G, Low WC, and Parr AM, Porcine to porcine blastocyst complementation to generate oligodendrocytes, Peyton Society 80th Anniversary Meeting, Minneapolis, MN 2017
• Crane A, Swaminathan P, Hewitt H, Xiao F, Savanur V, Voth J, Schultz Z, Carlson D, Fahrenkrug S, Dutton J, and Low WC, Use of blastocyst complementation in identifying novel source of tissue for craniofacial and neural regenerative therapies, Federation of European Neuroscience Society Annual Meeting, Copenhagen, Denmark, 2016

Presentations (Selected)

• 13th International Conference on Alzheimer’s and Parkinson’s, “Towards the Generation of Nigral Dopamine Neurons in Gene Edited Animals via Stem Cell Complementation for Treating Parkinson’s Disease,” Vienna, Austria, 2017
• 13th International Neural Transplantation and Repair Symposium, “Characterization of Chimeric Human-Porcine Blastocysts and PITX3 Knockout Swine for Generating Authentic Human Cells in the Pig,” Beijing, China, 2015
• Frontiers in Biomedical Research Symposium, “Stem Cells for Neural Repair,” Karolinska Institute, Stockholm, Sweden, 2010
• International Meeting of the Society for NeuroImmune Pharmacology, “State of the Art in Neural Stem Cell Biology,” Keynote Speaker, Wuhan, China, 2009
• International Symposium on Stem Cells and Transplantation, “Pluripotency and Neural Induction of Mesenchymal Stem Cells Derived from Adult Bone Marrow,” Nantes, France, 2003

Invited Oral Presentations (Selected)

• Cambridge HealthTech Institute, “Gene Editing for Generating Exogenic Organs and Cells,” Boston, MA 2016
• American Society for Neural Therapy and Repair, Workshop on Techniques for NeuroRepair, “Generating Authentic Neural Cells for Cellular Replacement and Repair,” Clearwater, FL 2016
• National Institutes of Health, Workshop on Animals Containing Human Cells, “Characterization of Human-Porcine Blastocysts and Fetuses,” Bethesda, MD, 2015
• Iowa State University, "Neural Induction of Bone Marrow-Derived Stem Cells," Ames, Iowa, 2003
• University of South Florida, “Neural Induction of Multipotent Adult Progenitor Cells (MAPCs) from Bone Marrow,” Tampa, Florida, 2003

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