Robert G Thorne, Ph.D.
5113 Rennebohm Hall (Labs: 5222/5224)
- Postdoc 2008 Neuroscience - New York University
- Ph.D. 2002 Pharmaceutics - University of Minnesota
- B.S. 1990 Chemical Engineering - University of Washington
Dr. Thorne's 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. 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.
Biological barriers to drug delivery and distribution; Drug action and design; Animal models of neurodegenerative disease and brain trauma
- 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-b 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, 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, W.H. Frey, II. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Research 692 (1-2): 278-282 (1995).