Preclinical findings of a recent study indicate that antimuscarinic drugs such as pirenzepine may be used to prevent or reverse symptoms of peripheral neuropathy. Antimuscarinic medications are often used for several other conditions, including peptic ulcers and incontinence.
Researchers note that the study results demonstrated the effectiveness of these medications in various aspects of peripheral neuropathy, “Our work shows for the first time the reversal of structural damage of nerve fibers in a mouse model of type 1 diabetes,” said senior study author Paul Fernyhough, the University of Manitoba and St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, Manitoba, Canada.
Peripheral neuropathy is a common condition that is caused by damage to one’s peripheral nervous system. It is linked to several conditions, including diabetes and medications such as chemotherapy. Symptoms include numbness, prickling, tingling, weakness, and pain in the extremities, and it can lead to amputation.
Dr. Fernyhough explained that the authors identified a novel endogenous pathway in adult neurons that regulates nerve fiber growth.
“Normally this pathway suppresses [the] growth of nerve fibers,” he said. “By use of antagonist drugs against a key receptor in the pathway, we are able to release the fibers from this constraint and permit higher levels of growth. This allows us to use specific drugs to drive nerve fiber regeneration and repair in disease states such as diabetes and chemotherapy where there is irreversible nerve damage.”
More specifically, researchers used antimuscarinics including pirenzepine to induce nerve fiber regeneration and repair in cell and rodent models of neuropathy associated with type 1 and type 2 diabetes, chemotherapy, and HIV.
“As a variety of antimuscarinic drugs are approved for clinical use against other conditions, prompt translation of this therapeutic approach to clinical trials is feasible,” the authors write. Dr. Fernyhough pointed out that, although this research is preclinical, phase 1 trials will begin this spring.
Further, “funding is in place to support 3 small proof of concept phase 2 clinical trials using a topical formulation of the drug to treat diabetic sensory neuropathy,” he added. These trials are expected to start later this year.
This research was published in The Journal of Clinical Investigation and was funded by grants from the Juvenile Diabetes Research Foundation, the Canadian Institutes of Health Research, and the National Institutes of Health. The authors also acknowledged St. Boniface Hospital Research Foundation for its support.—Meredith Edwards White
Calcutt NA, Smith DR, Frizzi K, et al. Selective antagonism of muscarinic receptors is
neuroprotective in peripheral neuropathy [Published online ahead of print January 17, 2017]. J
Clin Invest. doi: 10.1172/JCI88321.
Peripheral neuropathy: Overview. Mayo Clinic Website. https://www.mayoclinic.org/diseasesconditions/
peripheral-neuropathy/home/ovc-20204944. Published January 30, 2017.