UW-Madison School of Pharmacy

Navigation Options

head shot image

Robert G Thorne, PhD

Assistant Professor
Trainer - NTP, CNTP & CMP Training Programs; KL2 Scholar, ICTR

 

 

 


Dr. Thorne's research is currently focused on two primary goals: (i) To identify the factors affecting the short range diffusion and long range overall distribution of proteins, genes, viral vectors and nano­particles inside the developing, adult and pathologic central nervous system (CNS) and (ii) To identify the pathways and mechanisms allowing substances to enter the CNS following intranasal administation, a promising alternative route for CNS drug delivery.

Protein and gene therapies for CNS disorders like Alzheimer's disease, Parkinson's disease and stroke have been limited by two related yet distinct problems. The first concerns the difficulty associated with delivering a protein, gene or drug delivery vector into the CNS across the barriers that separate the blood from brain interstitial and cerebrospinal fluids. The second concerns the uncertainty surrounding what happens on the brain side of these barriers once a substance is able to pass them. Surprisingly, little infor­mation exists to predict the distribution of substances following their entry into the CNS. These problems have much to do with our current reliance on small molecule drugs to treat neurological illnesses; indeed, no CNS-acting biopharmaceutical product has yet received approval despite the existence of thousands of exceptionally promising protein and gene therapy candidates.

Dr. Thorne's diffusion work has focused on characterizing the diffusion properties of a variety of different substances in gels, brain slices and in vivo using optical imaging; this information is used to gain insights into what factors are important for drug distribution once inside the brain. Characterizing the diffusion properties of biopharmaceuticals is especially relevant for the design and enhancement of transvascular strategies for CNS drug delivery, particularly those involving nanoparticles, as well as convection enhanced drug delivery within the brain, a method of surgical infusion currently under test in clinical trials. Dr. Thorne's research on the intranasal route of administration has helped to elucidate how and why certain proteins, viruses, nanoparticles and even cells may reach the brain from the nasal passages in sufficient quantity to produce effects. A better understanding of the mechanisms, pathways and limitations for drugs capable of transport from the nasal passages to the brain will greatly aid in the successful application of this method; indeed, clinical trials to treat developmental disorders, neurodegenerative diseases and stroke are just beginning.

  • Council Member (Founding and Current), International Brain Barriers Society (IBBS), 2006-present
  • Editorial Board Member, Fluids and Barriers of the CNS (Biomed Central)
  • Faculty Representative, University of Wisconsin-Madison AAPS Student Chapter
  • Executive Committee Member (Chair), Graduate Program in Clinical Investigation, University of Wisconsin-Madison Institute for Clinical and Translational Research
  • Scientific Advisory Board Member, Research Initiative on Brain Barriers and Drug Delivery (Denmark), Lundbeck Foundation, 2013-present
  • Advisor, King's College London Blood-Brain Barrier Consortium with Industry, 2016-present

 

  • Faculty Advisor: Michelle Pizzo, BS (Pharm Sci PhD program); Niyanta Kumar, BS MS (Pharm Sci PhD program); Brynna Wilken-Resman, BS (Pharm Sci PhD program); Geetika Nehra, BS (Pharm Sci PhD program)
  • Postdoctoral Advisor: Jeff Lochhead, PhD

Professional Interests: Biological barriers to drug delivery and distribution; Drug action and design; Animal models of neurodegenerative disease and brain trauma

Education:

  • Postdoc 2008 Physiology & Neuroscience - New York University School of Medicine
  • PhD 2002 Pharmaceutics - University of Minnesota
  • BS 1990 Chemical Engineering - University of Washington

Other:

  • Elected Vice-President (President-elect), International Brain Barriers Society (IBBS), 2017-2018
  • Elected Chair, 2016 Gordon Research Conference - 'Barriers of the CNS'
  • Elected Vice-Chair, 2014 Gordon Research Conference - 'Barriers of the CNS'
  • NIH Special Emphasis Panel Member (2014)
  • International Scientific Committee Member. International Conference on Cerebral Vascular Biology. 8th (Sendai, Japan, 2009), 9th (Leiden, the Netherlands, 2011), 11th (Paris, France, 2015), and 12th (Melbourne, Australia, 2017) Conferences
  • Pharmacy 800 - Research Ethics (Course co-coordinator)
  • Pharmacy Practice 555 - Pharmacotherapy I
  • Pharmaceutical Sciences 421 - Introduction to Drug Delivery II
  • Pharmaceutical Sciences 540 - Drug Delivery Systems
  • Pharmaceutical Sciences 780 - Principles of Pharmaceutical Sciences
  • Neuroscience 611 - Systems Neuroscience
Highlighted Publications:
  • Kumar, N.N., M. Gautam, J.J. Lochhead, D.J. Wolak, V. Ithapu, V. Singh and R.G. Thorne. Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery. Scientific Reports 6, Article number: 31732 (2016).
  • Wolak, D.J., M.E. Pizzo, and R.G. Thorne. Probing the extracellular diffusion of antibodies in brain using in vivo integrative optical imaging and ex vivo fluorescence imaging. Journal of Controlled Release 197:78-86 (2015). FEATURED COVER STORY - Park, K. Antibody transport within the brain. Journal of Controlled Release 197:219 (2015).
  • Lochhead, J.J., D.J. Wolak, M.E. Pizzo, and R.G. Thorne. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration. Journal of Cerebral Blood Flow & Metabolism 35:371–381 (2015).
  • Hammarlund-Udenaes, M, E.C.M. de Lange, and R.G. Thorne (Editors). Drug Delivery to the Brain: Physiological Concepts, Methodologies and Approaches. Springer (AAPS Advances in the Pharmaceutical Sciences Series 10), 731 pages (2014).
  • Thorne, R.G. Primer on central nervous system structure/function and the vasculature, ventricular system, and fluids of the brain. IN: Drug Delivery to the Brain: Physiological Concepts, Methodologies and Approaches. Ed. Hammarlund-Udenaes, de Lange & Thorne. Springer, pages 685-707 (2014).
  • Lochhead, J.J. and R.G. Thorne. Intranasal drug delivery to the brain. IN: Drug Delivery to the Brain: Physiological Concepts, Methodologies and Approaches. Ed. Hammarlund-Udenaes, de Lange & Thorne. Springer, pages 401-431 (2014).
  • Wolak, D.J. and R.G. Thorne. Diffusion of macromolecules in the brain: implications for drug delivery. Molecular Pharmaceutics 10: 1492-1504 (2013).
  • Lochhead, J.J. and R.G. Thorne. Intranasal delivery of biologics to the central nervous system. Advanced Drug Delivery Reviews 64 (7): 614-628 (2012).
  • Thorne, R.G., A. Lakkaraju, E. Rodriguez-Boulan, and C. Nicholson. In vivo diffusion of lacto­ferrin in brain extracellular space is regulated by interactions with heparan sulfate. Proceedings of the National Academy of Sciences USA 105 (24): 8416-8421 (2008).
  • Thorne, R.G., L.R. Hanson, T.M. Ross, D. Tung, and W.H. Frey II. Delivery of interferon-beta to the monkey nervous system following intranasal administration. Neuroscience 152 (3): 785-797 (2008).
  • Thorne, R.G. and C. Nicholson. In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. Proceedings of the National Academy of Sciences USA 103 (14): 5567-5572 (2006).
  • Thorne, R.G., S. Hrabetova, and C. Nicholson. Diffusion measurements for drug design [Correspondence]. Nature Materials 4 (10): 713 (2005).
  • Thorne, R.G., S. Hrabetova, and C. Nicholson. Diffusion of epidermal growth factor in rat brain extracellular space measured by integrative optical imaging. Journal of Neurophysiology 96 (6): 3471-3481 (2004).
  • Thorne, R.G., G.J. Pronk, V. Padmanabhan, and W.H. Frey II. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 127 (2): 481-496 (2004).
  • Ross, T.M., P.M. Martinez, J.C. Renner, R.G. Thorne, L.R. Hanson, and W.H. Frey II. 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 151 (1-2): 66-77 (2004).
  • Thorne, R.G. and W.H. Frey II. Delivery of neurotrophic factors to the central nervous system: Pharmacokinetic considerations [Review]. Clinical Pharmacokinetics 40 (12): 907-946 (2001).
  • Liu, X.F., J.R. Fawcett, R.G. Thorne, and W.H. Frey II. Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusion. Neuroscience Letters 308 (2): 91-94 (2001).
  • Liu, X.F., J.R. Fawcett, R.G. Thorne, T.A. DeFor, and W.H. Frey II. Intranasal administration of insulin-like growth factor-1 bypasses the blood-brain barrier and protects against focal cerebral ischemic damage. Journal of the Neurological Sciences 187 (1-2): 91-97 (2001).
  • Frey, W.H. II, J. Liu, X.Q. Chen, R.G. Thorne, J.R. Fawcett, T.A. Ala, and Y-E. Rahman. Delivery of 125I-NGF to the brain via the olfactory route. Drug Delivery 4: 87-92 (1997).
  • Thorne, R.G., C.R. Emory, T.A. Ala, and W.H. Frey, II. Quantitative analysis of the olfactory path­way for drug delivery to the brain. Brain Research 692 (1-2): 278-282 (1995).