What is it about?

People with diabetes often develop nerve damage (neuropathy) that results in loss of sensation and also, in some cases, pain. We had already shown that a type of drug called a "muscarinic receptor antagonist" that is used to treat other diseases, caused sensory nerves to regrow in diabetic rodents. Rather than go through the long process of designing a new drug and the years of testing that is required before it can be tested in patients, we took advantage of an existing drug that is FDA-approved to treat overactive bladder, and which also happens to be a type of muscarinic receptor antagonist. US law allows physicians to use FDA-approved drugs for other purposes in what are called off-label studies. We therefore 1: tested the approved drug, oxybutynin, first in cells and then in diabetic rodents, to ensure it worked as well as those we had previously tested and then 2: tested the drug in patients with diabetes and nerve loss in the skin. We measured nerves in skin biopsies collected before treatment and after 5 months of daily treatment. The main finding was that treatment caused a significant increase in nerve density in the skin, whereas a placebo treatment did not. Patients also reported improvement of other aspects of their neuropathy including reduced pain and improved quality of life. We could not recommend that patients with diabetes start using this drug, as it was not designed for unsupervised, long term use, but the findings did encourage us to look into other more clinically viable options.

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Why is it important?

We believe that our study is the first to show than a drug treatment can make sensory nerves regrow in diabetic patients. It is also important that other aspects of diabetic neuropathy were improved at the same time, as pain and impaired quality of life are major real-world problems for diabetic patients. The positive findings of this proof-of-concept study encouraged us to develop a better version of the drug that could be safely used by patients for a longer time and to take that drug to new clinical trials (published in 2026).

Perspectives

The data reported this paper is intellectually satisfying to me as it shows that traditional preclinical research can predict drug efficacy in humans when designed and performed in a thoughtful manner. It also encouraged us to persevere with our efforts to establish a startup biotechnology company devoted to developing a more clinically viable version of the drug and to take that drug through the long and expensive process of FDA-mandated trials that must be overcome before the treatment can be made available to the public.

Nigel Calcutt
University of California San Diego

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This page is a summary of: A muscarinic receptor antagonist reverses multiple indices of diabetic peripheral neuropathy: preclinical and clinical studies using oxybutynin, Acta Neuropathologica, March 2024, Springer Science + Business Media,
DOI: 10.1007/s00401-024-02710-4.
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