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

Autor: Warren WG; Artelo Biosciences Ltd., Alderley Park, Alderley Edge, Cheshire, UK., Osborn M; Artelo Biosciences Ltd., Alderley Park, Alderley Edge, Cheshire, UK., David-Pereira A; Transpharmation Ltd., The London Bioscience Innovation Centre, London, UK., Tsantoulas C; Transpharmation Ltd., The London Bioscience Innovation Centre, London, UK., Xue W; Pharmaron Inc., Beijing, People's Republic of China., Yates A; Artelo Biosciences Ltd., Alderley Park, Alderley Edge, Cheshire, UK., OSullivan SE; Artelo Biosciences Ltd., Alderley Park, Alderley Edge, Cheshire, UK.
Jazyk: angličtina
Zdroj: European journal of pain (London, England) [Eur J Pain] 2024 Aug 26. Date of Electronic Publication: 2024 Aug 26.
DOI: 10.1002/ejp.4718
Abstrakt: 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.
(© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)
Databáze: MEDLINE
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