MRCT are collaborating with the University of Bristol to develop orally available small molecule TrkA antagonists for treatment of chronic intractable pain.
Nerve growth factor (NGF) is a key mediator in neuropathic and inflammatory pain via its receptor TrkA. Sequestration of NGF prevents pain in many conditions, and therapeutic antibodies aimed at neutralising NGF are currently in clinical trials. Antagonising NGF/TrkA interaction with small molecules could achieve similar efficacy without problems of delivery, antibody-related side effects and high cost.
Dr Shelley Allen and colleagues at the University of Bristol have validated the NGF/TrkA interaction as a therapeutic target, and identified a potential drug ‘specificity patch’ on TrkA. The project aims to generate lead compounds which bind to this patch, and validate them in models of pain.