Robert G. Thorne

Robert Thorne
Title
Assistant Professor, School of Pharmacy
Phone
(608) 890-3508
E-mail
rthorne@pharmacy.wisc.edu

Education:

Ph.D University of Minnesota

Research Focus:

CNS Drug Delivery and Distribution

Research Strengths:

Neurobiology of Disease; Molecular Neuroscience

Research Description:

My lab focuses 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 CNS and (ii) To identify the pathways and mechanisms allowing substances to enter the CNS following intranasal administration, 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. Our highly translational research addresses these problems using a multidisciplinary approach spanning neuroscience, pharmaceutics, biophysics, engineering and structural biology. Other interests include the use of neurotrophic factors, cytokines, siRNA and other biopharmaceutical products in animal models of disease, the design/optimization of protein conjugates, oligonucleotides, viral vectors and nanoparticles for CNS applications and blood-brain barrier modification strategies.

Present work in the laboratory is aimed at: (i) using integrative optical imaging, a method for measuring diffusion coefficients of fluorescently labeled substances, as a tool to provide valuable insights into the factors governing the diffusion of macromolecules and other large substances in the brain, e.g. the dimensions of the extracellular space (ECS) and the concentration of extracellular heparan sulfate binding sites important for many therapeutic proteins and vectors; (ii) exploring the diffusion properties of therapeutically important oligonucleotides (siRNA and antisense) and other biologics (proteins, nanoparticles, and viral gene therapy vectors) in brain ECS; (iii) using a combination of imaging and ultrastructural localization to determine the precise mechanisms and pathways underlying direct transport from the nasal passages to the CNS following intranasal administration; (iv) evaluating brain delivery and efficacy of various therapeutic agents in animal models of neurodegenerative disease following intranasal and other routes of administration.    

Publications:

Please see PubMed for most recent publications