ART26.12, a Novel Fatty Acid-binding Protein 5 Inhibitor, Shows Efficacy in Multiple Preclinical Neuropathy Models

Overview

Journal Eur J Pain

Publisher Wiley

Specialties Critical Care
Neurology
Psychiatry

Date 2024 Aug 27

PMID 39188040

Authors

W G Warren

M Osborn

A David-Pereira

C Tsantoulas

Wenwen Xue

A Yates

S E OSullivan

Affiliations

Soon will be listed here.

Abstract

Background: Painful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid-binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin-induced peripheral neuropathy.

Methods: In the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity.

Results: ART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel-induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin-induced diabetic neuropathy in male rats. In a model of breast cancer-induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment.

Conclusion: Overall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy.

Significance Statement: This work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management.

Citing Articles

ART26.12, a novel fatty acid-binding protein 5 inhibitor, shows efficacy in multiple preclinical neuropathy models.

Warren W, Osborn M, David-Pereira A, Tsantoulas C, Xue W, Yates A Eur J Pain. 2024; 29(2):e4718.

PMID: 39188040 PMC: 11671339. DOI: 10.1002/ejp.4718.

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