ArticleScientific reports2021
Repositioning of a novel GABA-B receptor agonist, AZD3355 (Lesogaberan), for the treatment of non-alcoholic steatohepatitis.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Drug Repurposing for Metabolic-Associated Fatty Liver Disease: Current Evidence, Challenges, and Future Perspectives.Drug design, development and therapy · 2026Review
- Primary Human Tissue Models for Metabolic Dysfunction-Associated Liver Disease - toward Streamlining Drug Discovery with Patient-Derived Assays.Advanced biology · 2025Review
- Ex Vivo Tools and Models in MASLD Research.Cells · 2024Review
- Kisspeptin Alleviates Human Hepatic Fibrogenesis by Inhibiting TGFβ Signaling in Hepatic Stellate Cells.Cells · 2024Article
- Repurposing of the analgesic Neurotropin for MASLD/MASH treatment.Hepatology communications · 2024Article
- MYC: there is more to it than cancer.Frontiers in cell and developmental biology · 2024Review
- Antifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach.Nature reviews. Gastroenterology & hepatology · 2023Review
- Review
- Gamma-Aminobutyric Acid Signaling in Damage Response, Metabolism, and Disease.International journal of molecular sciences · 2023Review
- FASN inhibition targets multiple drivers of NASH by reducing steatosis, inflammation and fibrosis in preclinical models.Scientific reports · 2022Article
- Hepatic fibrosis 2022: Unmet needs and a blueprint for the future.Hepatology (Baltimore, Md.) · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Non-alcoholic steatohepatitis (NASH) is a rising health challenge, with no approved drugs. We used a computational drug repositioning strategy to uncover a novel therapy for NASH, identifying a GABA-B receptor agonist, AZD3355 (Lesogaberan) previously evaluated as a therapy for esophageal reflux. AZD3355's potential efficacy in NASH was tested in human stellate cells, human precision cut liver slices (hPCLS), and in vivo in a well-validated murine model of NASH. In human stellate cells AZD3355 significantly downregulated profibrotic gene and protein expression. Transcriptomic analysis of these responses identified key regulatory nodes impacted by AZD3355, including Myc, as well as MAP and ERK kinases. In PCLS, AZD3355 down-regulated collagen1α1, αSMA and TNF-α mRNAs as well as secreted collagen1α1. In vivo, the drug significantly improved histology, profibrogenic gene expression, and tumor development, which was comparable to activity of obeticholic acid in a robust mouse model of NASH, but awaits further testing to determine its relative efficacy in patients. These data identify a well-tolerated clinical stage asset as a novel candidate therapy for human NASH through its hepatoprotective, anti-inflammatory and antifibrotic mechanisms of action. The approach validates computational methods to identify novel therapies in NASH in uncovering new pathways of disease development that can be rapidly translated into clinical trials.
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Registered trials
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