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Novel analgesics based on antagonism of TRPV1-AKAP79 binding

Reference	BB/N022181/1
Principal Investigator / Supervisor	Dr Katherine Stott
Co-Investigators / Co-Supervisors	Professor Peter Anthony McNaughton
Institution	University of Cambridge
Department	Biochemistry
Funding type	Research
Value (£)	732,820
Status	Completed
Type	Research Grant
Start date	01/09/2016
End date	31/12/2019
Duration	40 months

Abstract

unavailable

Summary

Pain is a significant clinical problem, because all existing analgesics have major side effects and are also poorly effective in many clinically important types of pain. A membrane ion channel, TRPV1, which is activated by heat, is critical for pain because when tissues are damaged, inflammatory mediators lower the temperature threshold of TRPV1 so that it can be activated even by normal body heat and thus cause ongoing pain. We have discovered how to prevent the effects of inflammatory mediators on TRPV1. A scaffolding protein, AKAP79, forms a "basket" structure which holds close to TRPV1the enzymes responsible for lowering its threshold. We have identified the binding site and can prevent binding using competitor peptides. These peptides give good analgesia in a mouse models of pain, including in a model of diabetic neuropathy, an intractable human pain condition. We will develop improved TRPV1-AKAP79 blocking peptides as better analgesics for intractable forms of pain.

Committee	Not funded via Committee
Research Topics	Neuroscience and Behaviour, Pharmaceuticals, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	Follow-On Fund Super (SuperFOF) [2012-2015]
Funding Scheme	X – not Funded via a specific Funding Scheme

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