CBS Seminar: Paul Fernyhough- Antagonism of muscarinic receptors drives peripheral nerve repair to reverse neuropathic disease in rodents and humans

Abstract:

Distal dying-back of nerve fibers is observed in many diseases including diabetic neuropathy, chemotherapy-induced peripheral neuropathy (CIPN) and human immunodeficiency virus (HIV)-associated neuropathy. The impact on human health is significant and rising. There are no therapies for any of these neuropathies. Our recent studies have revealed a novel therapeutic target for preventing and even reversing neuropathy-induced nerve loss. We have found that muscarinic acetylcholine type 1 receptors (M1Rs) regulate sensory axonal plasticity. We have discovered that antimuscarinic drugs selective or specific for the M1R can drive axonal outgrowth and prevent/reverse neurodegeneration in rodent models of peripheral nerve disease. I will discuss the multiple mechanisms triggered by antimuscarinic drug action at the M1R to modulate ion channel function and enhance neuronal metabolism and axonal outgrowth. Furthermore, I will present data from a recent Food and Drug Administration (FDA)-approved phase 2 clinical trial in persons with type 2 diabetes and mild-moderate diabetic neuropathy revealing significantly improved quality of life (Norfolk-QOL-diabetic neuropathy total score) and raised nerve fiber levels in skin in response to 6 months of topical delivery of the M1R selective drug, pirenzepine.

Bio: Paul performed PhD in biochemistry in the department of Biochemistry at University of Sheffield. Then carried out postdoctoral research at Colorado State University, Kings College London and as a Wellcome Trust Postdoctoral Fellow at St Bartholomew’s Medical College and then Queen Mary and Westfield College. He subsequently worked as a tenured lecturer in the School of Biological Sciences at the University of Manchester. Dr. Fernyhough moved to Winnipeg in 2004 and contributed to setting up a neuroscience research group at St Boniface Hospital Albrechtsen Research Centre and holds a tenured professorship in the Department of Pharmacology & Therapeutics at University of Manitoba. Dr. Fernyhough’s research interest is in the cell biology underlying neurodegenerative disorders of the peripheral nervous system with a focus on the impact of diabetes. A biotech start-up, WinSanTor Inc, has been established and is directing phase 2 clinical trials in diabetic neuropathy and chemotherapy-induced peripheral neuropathy.