{"id":"07575","slug":"anti-angptl3-treatment-for--07575","source":{"id":"07575","dataset":"techtransfer","title":"Anti-ANGPTL3 Treatment for Cardiometabolic Disease","description_":"<p>A University of Pittsburgh researcher has identified a novel treatment strategy for cardiometabolic disease, including heart failure with preserved ejection fraction (HFpEF). Building on a recent discovery that factors expressed from the heart can drive liver dysfunction and promote HFpEF progression, the invention provides methods of treating HFpEF — and HFpEF associated with liver disease — by administering an inhibitor of angiopoietin-like protein 3 (Angptl3), such as a monoclonal antibody or other targeted approach. This strategy could halt HFpEF progression and dramatically improve outcomes for those living with the disease.</p><p><h2>Description</h2>HFpEF is responsible for over half of all heart failure cases in the United States. Despite this high prevalence, no HFpEF specific medications exist with current treatment strategies focused on the management of comorbidities known to promote HFpEF progression (e.g., obesity and type 2 diabetes). Previous work has identified the role of liver dysfunction in HFpEF progression. With the recent discovery of a novel heart-to-liver signaling pathway as a potential therapeutic target, the lipid metabolism regulator Angptl3, has been identified. Inhibition of Angptl3 expression can directly treat HFpEF and could revolutionize the treatment of the millions of patients living with cardiometabolic disease.</p><p><h2>Applications</h2>-\tCardiometabolic disease e.g., heart failure with preserved ejection fraction (HFpEF)\r<br>-\tMetabolic dysfunction-associated liver disease (MASLD)\r<br>-\tCombination cardiac-hepatic indication  \r<br>-\tDiagnostic or patient-stratification use</p><p><h2>Advantages</h2>Direct treatment of HFpEF is an unmet clinical need. Currently, clinicians treat comorbidities and risk factors to reduce HFpEF progression. This approach fails to treat the underlying cause of HFpEF and risks adverse events due to polypharmacy. \r<br> \r<br>Recent work identified Gcn5l1 as a protective heart-specific factor. In mice models of HFpEF when Gcn5l1 is deleted from cardiomyocytes (cKO), cardiac dysfunction was exacerbated. Of note, cKO mice increased the expression of a key lipid metabolism regulator, Angptl3, disrupting Angptl3-regulated lipase activity, resulting in cholesterol-mediated liver steatosis. This novel treatment approach directly inhibits Angptl3 expression and can directly modify the course of HFpEF progression.</p><p><h2>Invention Readiness</h2>In cKO mice, elevated levels of Angptl3 were discovered in the hearts and livers of HFpEF mice resulting in reduction in both lipoprotein lipase (LPL) production and activity and other proteins responsible for cholesterol metabolism. In wildtype (WT) HFpEF mice, treatment with evinacumab, an Angptl3 inhibitor, rebalanced the Angptl3-LPL axis, reduced cardiac fibrosis, normalized liver cholesterol and liver weight, halted body weight progression, and improved insulin sensitivity. Further work is required to explore other Angptl3 inhibitors, including decoy receptors or gene therapies.</p><p><h2>IP Status</h2>Patent Pending</p><p><h2>Related Publication(s)</h2><p>Bugga, P., Mushala, B. A., Stoner, M. W., Manning, J. R., Bhattarai, N., Sharifi-Sanjani, M., Vandevender, A., Mooli, R. G., Ramakrishnan, S. K., Kaufman, B. A., Shiva, S. S., Happe, C. L., Mullet, S. J., Gelhaus, S. L., Jurczak, M. J., &amp; Scott, I. (2025). Cardiac-specific GCN5L1 deficiency promotes MASLD in HFpEF. bioRxiv (Cold Spring Harbor Laboratory). <a href=\"https://doi.org/10.1101/2025.02.05.636634\" rel=\"noopener noreferrer\" target=\"_blank\" style=\"color: rgb(9, 79, 209);\"><u><a target=\"_blank\" href=\"https://doi.org/10.1101/2025.02.05.636634\">https://doi.org/10.1101/2025.02.05.636634</a></u></a></p><p>Stewart, J. E., Islam, R., Meadows, E., Mogus, J. P., Velayutham, M., Khramtsov, V. V., Scott, I., Hollander, J. M., &amp; Thapa, D. (2026). GCN5L1-Mediated Lysine Acetylation Regulates Mitochondrial Bioenergetics and Redox Homeostasis in the Aged Heart. Antioxidants (Basel, Switzerland), 15(4), 481. <a href=\"https://doi.org/10.3390/antiox15040481\" rel=\"noopener noreferrer\" target=\"_blank\" style=\"color: rgb(9, 79, 209);\"><u><a target=\"_blank\" href=\"https://doi.org/10.3390/antiox15040481\">https://doi.org/10.3390/antiox15040481</a></u></a></p></p>","tags":["Antibody - mAb","Drug Discovery - Target","Life Science"],"file_number":"07575","collections":[{"key":517,"name":"Cardiometabolic"}],"meta_description":"Angptl3 inhibitors offer a targeted HFpEF therapy, linking heart-to-liver signaling to halt disease progression and improve metabolism.","image_url":"","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":3.0,\"scalability\":3.0,\"timeliness\":4.0},\"weighted_score\":3.9,\"risks\":[\"Preclinical only with limited translational data\",\"Unknown long-term safety of Angptl3 inhibition in diverse cardiometabolic contexts\",\"Potential competition from existing Angptl3 inhibitors or alternative pathways\",\"Regulatory path for combination with liver disease comorbidities\"],\"one_sentence_take\":\"Promising novelty and impact with solid preclinical readiness, but translational and regulatory risks temper near-term scalability.\"}","lead_inventor_name":"Iain Scott","lead_inventor_dept":"Med-Medicine","technology_type":"Therapeutic Modality","therapeutic_areas":["Hepatology","Cardiovascular"],"therapeutic_indications":["Metabolic Associated Fatty Liver Disease (MAFLD)","Heart failure"],"custom_tags":[],"all_tech_innovators":["Iain Scott"],"date_submitted":"2026-04-27"},"highlight":{},"matched_queries":null,"score":0.0}