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Humanizing Dyslipidemia in MASH: A PCSK9-Driven dyslipidemia GAN DIO-MASH Model

  • Henrik

Background & aim: Dyslipidemia, characterized by hyper-cholesterolemia and hypertriglyceridemia, is a central component of metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis. While being highly instrumental in drug development, preclinical models of MASH often fail to recapitulate a human-like lipoprotein profile. To enhance…

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Single-Cell Transcriptomic Profiling of MASH-HCC Development

  • Allison Butt

Background & aim: Bulk RNA-sequencing has limited cellular-level insight into metabolic-associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma (HCC) by masking rare and tumor-relevant populations. Here, we used single-cell transcriptomics to characterize liver cell-specific transcriptomic changes in the GAN…

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Semaglutide improves metabolic and histological outcomes and reverses clinically relevant biomarker alterations in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH

  • Barbora Krajnikova

Background & aim: The long-acting glucagon-like peptide-1 (GLP1) receptor agonist semaglutide was recently approved as the first GLP-1–based therapy for people with MASH and moderate-to-severe fibrosis. Clinical studies have demonstrated that semaglutide not only improves liver histology but also reverses…

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Therapeutic efficacy, biomarker signatures, and translatability of semaglutide in the liver biopsy-confirmed GAN DIO-MASH mouse model

  • Henrik

Background & aim: Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising therapeutic candidates for metabolic dysfunction-associated steatohepatitis (MASH). Importantly, semaglutide was recently approved as the first GLP-1-based treatment for people with MASH with moderate-to-severe fibrosis. Translational models that recapitulate…

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Targeting nuclear envelope improves NAFLD Activity Score and shows antifibrotic and hepatoprotective effects superior to Lanifibranor in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH

  • Allison Butt

Background & aim: NLT-101 is a first-in-class compound that functions by proximity engagement with a target in the nuclear envelope that mediates its activity. NLT-101 is in preclinical development for metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis driven indications. The present…

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