Systemic inhibition of soluble TNF significantly changes glial cell populations leading to improved myelin integrity and better functional outcome after experimental stroke
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Proof-of-concept testing of semaglutide in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH
Background & aim: The long-acting glucagon-like peptide-1 (GLP-1) analogue semaglutide is approved for the treatment of type 2 diabetes and obesity. Recently, semaglutide has been reported to improve liver histopathological outcomes in patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis…
Superior Hepatoprotective Effects of OPK-88006, a Novel GLP-1/Glucagon receptor dual agonist, to Semaglutide and Survodutide in the GAN Diet-Induced Obese and Biopsy-Confirmed Mouse Model of MASH
Background & aim: OPK-88006 is a novel peptide-based, long-acting glucagon-like peptide-1 receptor (GLP1R)/glucagon receptor (GCGR) dual agonist in current preclinical development for metabolic diseases, including obesity and metabolic dysfunction-associated steatohepatitis (MASH). The present study aimed to compare the therapeutic profile…
Tirzepatide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH-HCC with advanced fibrosis
Background & aim: The glucagon-like peptide-1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR) dual agonist tirzepatide is currently approved for the treatment of obesity and type 2 diabetes. In a recent phase 2b trial (SYNERGY-NASH) in patients with metabolic-dysfunction…
Metabolic effects of survodutide in DIO mice at thermoneutrality
Background & aim: Survodutide is a dual agonist of the glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), currently in clinical development for obesity and related metabolic disorders. By concurrently enhancing GCGR and GLP1R signaling, survodutide offers a synergistic approach…
GUBox, a dual Ox1R/Ox2R peptide agonist, promotes wakefulness and reduces cataplexy in orexin/ataxin3 mice
Aim: Utilize orexin analogues to activate central orexin signaling and compensate for the loss of endogenous orexin function in Narcolepsy Type 1 (NT1). How? Engineering highly potent dual orexin receptor (OxR) 1 and OxR2 agonists from orexin backbone with optimized…
Development and characterization of a humanized GLP-1 receptor mouse model for translational drug development
Background & aim: Injectable peptide-based GLP-1 receptor agonists (GLP1RAs) are effective treatments for obesity and type 2 diabetes, yet present challenges related to patient compliance and scalable production. In contrast, small-molecule GLP1RAs offer significant advantages, including oral bioavailability and scalable…
Single-cell Transcriptomic Profiling of MASH-HCC Development
Background & aim: Cellular-level insights into metabolic associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma (HCC) have been limited by bulk RNA-sequencing, which masks rare or tumor-relevant populations. Here, we applied single-cell transcriptomics to characterize liver cell-specific transcriptome changes…