Treatments for peripheral neuropathy, the numbness and pain most commonly felt in the fingers, arms and legs due to nerve damage, tend to focus on managing pain. But an international team may have found an alternative approach that could potentially reverse symptoms with a class of drugs already in use for other conditions.
Addressing the underlying condition behind neuropathy—such as diabetes—is a major part of alleviating symptoms, but there is no approved treatment that focuses on nerve degeneration. While studying mechanisms involved in neuron growth and regrowth, scientists from UC San Diego and the University of Manitoba, alongside colleagues from St. Boniface Hospital and the National Institute of Diabetes and Digestive and Kidney Diseases, identified a pathway that stunts the outgrowth of neurites, which connect neurons to other neurons.
The activation of muscarinic acetylcholine receptors inhibits the growth of sensory neurons. The team found that blocking this pathway reversed the effects of peripheral neuropathy in mouse models of Type 1 and 2 diabetes, HIV and chemotherapy-induced neuropathy. Their findings were published in the Journal of Clinical Investigation.
The best part? A number of antimuscarinic drugs, such as atropine and pirenzepine, are already approved and on the market for other indications, ranging from incontinence to peptic ulcers. This could lead to a potentially speedy path to clinical use.
Paul Fernyhough of the University of Manitoba and St. Boniface Hospital, Nigel Calcutt of UC San Diego and Lakshmi Kotra of the University of Toronto have cofounded the company WinSanTor to continue working on this approach.
The biotech has exclusively licensed the technology from the researchers and has come up with a repurposed and reformulated version of an already-approved drug, dubbed WST-057. The candidate has prevented and reversed nerve fiber depletion and sensory loss in animal models of peripheral neuropathy, according to a statement.
“An exciting aspect of this work is that these are new uses for old drugs. They have been used in humans for over 20 years with no serious side effects and have an excellent safety profile. We expect Phase 1 trials to progress smoothly with Phase 2 trials arranged and already funded for 2017,” said Fernyhough in a statement.