Differential Therapeutic Profile of Efruxifermin in the GAN DIO-MASH and CDAA-HFD Mouse Models of MASH
Background & aim: Fibroblast growth factor 21 (FGF21) plays a key role in hepatic lipid metabolism and holds great promise as therapeutic target for metabolic dysfunction-associated steatohepatitis (MASH). Efruxifermin (EFX) is a long-acting FGF21 analogue currently inphase 3 clinical development for pre-cirrhotic…
A Multimodal Rat Brain Atlas and Whole-Brain Imaging Pipeline for Mapping Satiety Pathways and Anti-Obesity Drug Effects
Background & aim: Central regulation of appetite and satiety engages neuronal populations distributed across the brain. The identification of novel drug targets, development of anti-obesity therapeutics, and validation of their mode of action benefit from whole-brain imaging. Light-sheet fluorescence…
Nintedanib lacks efficacy in a spirometry-confirmed and bleomycin-induced mouse model of idiopathic pulmonary fibrosis
Abstract: Nintedanib, a multitargeted tyrosine kinase inhibitor, is approved for idiopathic pulmonary fibrosis (IPF) for its ability to slow lung function decline. This study systematically evaluated the effects of nintedanib across three independent treatment intervention studies in the single-dose bleomycin…
AI-driven whole-brain cellular profiling using 3D microscopy
Background & aim: Neurodegenerative diseases are characterized by complex, large-scale structural and cellular alterations across the brain. Understanding these changes requires comprehensive, whole-brain analysis at high spatial resolution. Three-dimensional light sheet fluorescence microscopy (3D LSFM) enables rapid imaging of intact…
High-throughput 3D whole-brain imaging reveals sex-dependent parenchymal and vascular amyloid plaque architecture in a standard mouse model of Alzheimer’s disease
Background & aim: Alzheimer’s disease (AD) is histologically defined by accumulation of Abeta (Ab) plaques in the brain. Age and gender are important factors in AD pathology. To develop more effective interventions, preclinical studies should therefore consider these factors in…
Whole-brain 3D quantification of aSyn spreading and dopaminergic neurodegeneration in a mouse model of Parkinson’s disease
Background & aim: Progressive spreading of pathological alpha‑synuclein (αSyn) aggregates in the brain drives the degeneration of tyrosine hydroxylase (TH)-positive dopaminergic neurons in Parkinson’s disease (PD). Development of disease-modifying therapies has been hampered by the lack of techniques that can…
Survodutide acts through circumventricular organs in the brain and activates neuronal regions associated with appetite regulation
Abstract: Survodutide is a novel GCG/GLP-1 receptor (GCGR/GLP-1R) dual agonist in clinical development for people with obesity and people with metabolic dysfunction-associated steatohepatitis (MASH). Preclinically, survodutide demonstrated body weight lowering efficacy through decreased energy intake and increased energy expenditure. Here,…
Generation and characterisation of a humanised GLP-1 receptor mouse model for translational drug development
Background: Injectable peptide-based glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RAs) are effective treatments for obesity and diabetes but are limited by patient compliance and scalability challenges. In contrast, non-peptide small-molecule GLP1RAs offer the advantage of oral delivery but are relatively inactive…