In situ production of analgesic peptides for the treatment of joint pain

Osteoarthritis is the most common, debilitating form of arthritis. Current treatments for osteoarthritis provide inadequate pain control, and there is a need for new therapies for chronic joint pain. Experimental and clinical evidence suggests that osteoarthritic pain is driven and maintained through ongoing peripheral nociceptive input. This project aims to block the ongoing nociceptive input by utilizing gene therapy to locally produce recombinant analgesic peptides within the joint. The researcher, Dr. Tony Lim, will carry out a preclinical proof-of-concept study in the Department of Pharmacology at the University of Cambridge under the supervision of Dr. Ewan Smith and will: 1) Generate an AAV-based vector that drives secretion of functional recombinant ProToxin-II (a spider venom peptide that blocks voltage-gated sodium channel 1.7 and possesses analgesic properties) in synoviocytes, 2) determine whether ProToxin-II secreting synoviocytes inhibit sensory neuron activity in an in vitro arthritic pain model, and 3) evaluate the effectiveness and safety of ProToxin-II gene therapy in preclinical models of arthritic pain. As part of this research, the researcher will also visit the Scuola Internazionale Superiore di Studi Avanzati under the supervision of Prof. Paul Heppenstall to assist in the generation of viral tools. This work has the potential to kickstart a novel gene therapy for the treatment of joint pain.