Treatment with the anti-Angptl4 monoclonal antibody 14D12 reduced fasting serum triglycerides by 50% to 59% in mice, recapitulating the lipid phenotype of Angptl4 knockout mice.
Effect estimate: 50-59% reduction
p-value: p=<0.0001
We used gene knockout mice to explore the role of Angiopoietin-like-4 (Angptl4) in lipid metabolism as well as to generate anti-Angptl4 mAbs with pharmacological activity. Angptl4 -/- mice had lower triglyceride (TG) levels resulting both from increased very low-density lipoprotein (VLDL) clearance and decreased VLDL production and had modestly lower cholesterol levels. Also, both Angptl4 -/- suckling mice and adult mice fed a high-fat diet showed reduced viability associated with lipogranulomatous lesions of the intestines and their draining lymphatics and mesenteric lymph nodes. Treating C57BL/6J, ApoE -/-, LDLr -/-, and db/db mice with the anti-Angptl4 mAb 14D12 recapitulated the lipid and histopathologic phenotypes noted in Angptl4 -/- mice. This demonstrates that the knockout phenotype reflects not only the physiologic function of the Angptl4 gene but also predicts the pharmacologic consequences of Angptl4 protein inhibition with a neutralizing antibody in relevant models of human disease.
Desai et al. (Tue,) conducted a other in Hypertriglyceridemia. anti-Angptl4 mAb 14D12 vs. Control mAb or vehicle was evaluated on Fasting serum triglyceride levels (50-59% reduction, p=<0.0001). Treatment with the anti-Angptl4 monoclonal antibody 14D12 reduced fasting serum triglycerides by 50% to 59% in mice, recapitulating the lipid phenotype of Angptl4 knockout mice.