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…
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,…
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…
Background & aim: Glucagon-like peptide-1 receptor agonists, such as semaglutide, induce substantial weight loss but may adversely affect muscle mass. This is of particular concern in older adults with obesity, who are vulnerable to sarcopenia. Accordingly, obesity treatments should be…
Background & aim: Polycystic ovary syndrome (PCOS) affects approximately 10–15% of women of reproductive age and is a leading cause of anovulation and infertility. PCOS is frequently accompanied by hyperandrogenism, insulin resistance, and altered body composition. Androgen-induced mouse models reproduce…
Background & aim: Subcutaneous pump delivery of the GLP1-receptor-agonist exenatide reduced body weight and improved glycemia in the DIO mouse. Basal-bolus administration conferred advantage over basal alone. This mode of incretin-based therapy offers an alternative to conventional intermittent dosing and…
Background & aim: Accurate assessment of muscle mass remains a major challenge in preclinical models of sarcopenia, obesity, and drug-induced atrophy. Traditional readouts such as lean mass from body composition scans lack spatial resolution and anatomical specificity, especially in conditions…
Background & aim: Translational rodent models of glomerulosclerosis are essential in drug discovery for chronic kidney disease (CKD). The anti-glomerular basement membrane (anti-GBM) model in mice represents a clinically relevant model as it exhibits key features of albuminuria and glomerulosclerosis.…
Background & aim: Transferrin receptor-1 (TfR1) transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders. In this study, we investigated brain delivery and effects on plaque burden of…
