Peer-Reviewed Phase 2a Trial Demonstrates Peripheral Nerve Regeneration in Diabetic Neuropathy

On December 5, 2025, eBioMedicine (The Lancet Discovery Science) published the results of a randomized, double-blind, placebo-controlled Phase 2a clinical trial evaluating WST-057 (4% topical pirenzepine) in 58 patients with painful diabetic peripheral neuropathy across five Canadian academic medical centers. The study was led by independent investigators and evaluated a once-daily topical therapy designed to restore peripheral nerve function rather than simply reduce pain. The therapeutic approach originated from the discovery that activation of the muscarinic M1 receptor creates a “cholinergic brake” that suppresses mitochondrial function and limits the ability of damaged peripheral nerves to regenerate. By selectively blocking this receptor, WST-057 restores the cellular energy required for nerve repair and regeneration. Patients treated once daily for 24 weeks demonstrated statistically significant regeneration of intraepidermal nerve fibers at the ankle compared with placebo (primary endpoint; p = 0.012 overall; p = 0.006 in the higher-dose group), together with a 10.4-point improvement in Norfolk Quality of Life (QoL-DN) scores (p < 0.001) in the per-protocol population. The study also reported improvements in sural nerve conduction velocity that reached the threshold considered clinically meaningful and was supported by complementary preclinical data demonstrating restoration of nerve structure and function. The authors conclude that diabetic peripheral neuropathy remains a disease with no effective definitive treatment. These findings support a potential shift from symptom management toward disease modification through peripheral nerve regeneration, providing peer-reviewed clinical evidence that repairing damaged peripheral nerves may be achievable.

For decades, peripheral neuropathy has been treated as an irreversible disease. Physicians have had few options beyond managing pain while patients progressively lose sensation, balance, mobility, and independence. Today, peripheral neuropathy affects nearly half of all people with diabetes, millions of cancer survivors following chemotherapy, and many patients living with HIV and other neurological disorders, creating an enormous medical, societal, and economic burden. This peer-reviewed publication reports objective clinical evidence that damaged peripheral nerves can regenerate in humans. If confirmed in larger studies, it challenges one of the longest-standing assumptions in neurology—that damaged peripheral nerves cannot be meaningfully repaired—and suggests a future in which treatment focuses on restoring nerve function rather than simply managing symptoms. The implications extend beyond diabetic neuropathy and could influence how peripheral nerve damage is treated across multiple diseases.

This research has the potential to change the lives of millions living with peripheral neuropathy—people with diabetes trying to avoid falls, ulcers, and amputations; cancer survivors left with permanent nerve damage after chemotherapy; people living with HIV and other neurological disorders; and older adults struggling to maintain mobility and independence. Often called an “invisible disease,” peripheral neuropathy quietly steals sensation, balance, dexterity, sleep, confidence, and the ability to perform everyday tasks. Families and caregivers watch loved ones gradually lose their independence while physicians have had few options beyond symptom management. If damaged peripheral nerves can be regenerated, the impact extends far beyond one disease. It could fundamentally change how patients, physicians, and healthcare systems think about aging, disability, survivorship, and recovery—shifting the conversation from adapting to nerve loss to restoring nerve function.

Human clinical evidence: In a randomized, double-blind, placebo-controlled Phase 2a trial, patients treated with topical WST-057 showed statistically significant increases in intraepidermal nerve fiber density compared with placebo, providing objective biopsy evidence of peripheral nerve regeneration. The higher-dose group gained 2.32 nerve fibers/mm from baseline (p = 0.006), and the combined treatment groups differed significantly from placebo (p = 0.012). The per-protocol population also showed a 10.4-point improvement over placebo in Norfolk QoL-DN scores (p < 0.001). Mechanistic foundation: Earlier research published in the Journal of Clinical Investigation showed that blocking the muscarinic M1 receptor enhanced neurite growth, activated AMPK, overcame diabetes-related mitochondrial dysfunction, and prevented or reversed structural and functional signs of neuropathy in multiple preclinical models. The findings extended beyond diabetes to models of chemotherapy- and HIV-associated neuropathy. Independent scientific validation: The clinical study was conducted through five Canadian academic medical centers and published after peer review in eBioMedicine, part of The Lancet Discovery Science portfolio. The broader program has also received repeated competitive funding from NIH, JDRF, CIHR, and other public research agencies. Evidence of patient interest: Patients have followed pirenzepine and WST-057 in Mayo Clinic Connect discussions since at least 2019, repeatedly asking about trial results, availability, Expanded Access, and Phase 3 development. One participant wrote, “I have researched it and it sounds very promising,” while others described the program as one of the few efforts focused on nerve repair rather than pain relief.

Read the peer-reviewed publication, follow the progress of WST-057, and register for updates on future Phase 3 clinical trials and planned patient access initiatives—including Right to Try and Expanded Access—at WinSanTor.com.