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Targeted delivery of glycine receptors to peripheral neurons as treatment for pain

详细技术说明

None

*Abstract

The inventors have shown that HSV-directed expression of GlyR (glycine receptor) in peripheral neurons and subsequent selective activation has the potential to be used therapeutically for pain management. These results are particularly relevant in that neuropathic pain, a common consequence of damage to the peripheral nervous system, is debilitating and current medical management remains inadequate in treating this pain. More generally, these studies suggest that targeted transgene delivery of GlyR may have broad utility in selective modulation of neuronal activity. Given our knowledge of Cys-loop receptor structure and function, GlyR responsiveness and the robustness of its activity may be finely tuned via mutagenesis and/or exogenous application of agonists, antagonists, pharmacologic agents, and allosteric modulators, offering a novel and potentially powerful treatment to alter neuronal polarization of targeted populations of excitable cells. Applications:1) Treatment for pain especially for neuropathic type2) May have broad utility in selective modulation of neuronal activity3) Treatment of neurological disordersAdvantages:1) No effective treatment for chronic pain particularly neupathic, which is a common consequence of damage to the peripheral nervous system 2) No deleterious side effects3) Pain therapy may be modulated by drugs specific for the receptorStage of Development:1) Proven in vitro delivery of functional receptor. 2) In vivo studies in rat formalin pain model show complete elimination of pain response upon receptor activation, reversed by addition of specific antagonist that also targets the same receptor.

*Principal Investigation

Name: Michael Cascio, Associate Professor

Department: Med-Microbiology and Molecular Genetics

Name: Joseph Glorioso, Professor & Chairman

Department: Med-Microbiology and Molecular Genetics

Name: James Goss, Research Assistant Professor

Department: Neuroscience

Name: David Krisky

Department: Med-Pathology

国家/地区

美国