Robert G. Thorne, PhD

Portrait of Robert G. Thorne, PhD
Assistant Professor
Pharmacy
Address: 
5113 Rennebohm
777 Highland Ave
Madison, WI 53705
Telephone: 
(608) 890-3508
Focus Groups: 
Neuroscience/Neuropathology
Education: 
PhD, Pharmaceutics, University of Minnesota
Post-doctoral, Physiology & Neuroscience, New York University School of Medicine
Research Summary: 
CNS drug delivery; transport mechanisms in brain tissue; neurodegenerative disease, multiple sclerosis & stroke
Research Detail: 

Our research is currently focused on two primary goals: (i) To identify the factors affecting the diffusion 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. Our research focuses on the study of diffusive and convective transport within the extracellular and perivascular spaces of the central nervous system and the development, refinement, and optimization of strategies for delivering proteins, genes, viral vectors and nano­particles into the brain. We aim to leverage knowledge of physiology and central nervous system structure with state-of-the-art in vivo imaging methods in order to identify new ways to effectively deliver drugs to the brain and to better understand how endogenous proteins such as antibodies distribute within the central compartment.

In addition to his research program, Dr. Thorne serves on the editorial board of Fluids and Barriers of the CNS and is a founder and Council/Steering Committee member of the International Brain Barriers Society (http://www.ibbsoc.org/) as well as the elected 2016 Chair and organizer for the “Barriers of the CNS” Gordon Research Conference (http://www.grc.org/programs.aspx?id=12833).

Our 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. Our 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.

Selected Publications: 
Wolak, D.J., M.E. Pizzo, & 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).
Lochhead, J.J., D.J. Wolak, M.E. Pizzo, & 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.L. de Lange, & R.G. Thorne (Ed.) Drug Delivery to the Brain: Physiological Concepts, Methodologies & Approaches. Springer (Berlin), 731 pp. (2014).
Wolak, D.J. & R.G. Thorne. Diffusion of macromolecules in the brain: implications for drug delivery. Molecular Pharmaceutics 10:1492-504 (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., L.R. Hanson, T.M. Ross, D. Tung and W.H. Frey II. Delivery of interferon-b to the monkey nervous system following intranasal administration. Neuroscience 152 (3): 785-797 (2008).
Thorne, R.G., A. Lakkaraju, E. Rodriguez-Boulan, and C. Nicholson. In vivo diffusion of lacto-ferrin 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. 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. Nature Materials 4 (10): 713 (2005).
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., 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).
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).
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).
Lochhead, J.J. and R.G. Thorne. Intranasal delivery of biologics to the central nervous system [review]. Advanced Drug Delivery Reviews (in press).
Thorne, R.G., L.R. Hanson, T.M. Ross, D. Tung and W.H. Frey II. Delivery of interferon-b to the monkey nervous system following intranasal administration. Neuroscience 152 (3): 785-797 (2008).
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. 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).
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., 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).
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).