AAV-Mediated ApoC2 Gene Therapy: Reversal of Severe Hypertriglyceridemia and Rescue of Neonatal Death in ApoC2-Deficient Hamsters.

Abstract

Apolipoprotein C2 (ApoC2) is a key activator of lipoprotein lipase for plasma triglyceride metabolism. ApoC2-deficient patients present with severe hypertriglyceridemia and recurrent acute pancreatitis, for whom the only effective treatment is the infusion of normal plasma containing ApoC2. However, since ApoC2 has a fast catabolic rate, a repeated infusion is required, which limits its clinical use. To explore a safe and efficient approach for ApoC2 deficiency, we herein established an adeno-associated virus expressing human ApoC2 (AAV-hApoC2) to evaluate the efficacy and safety of gene therapy in ApoC2-deficient hypertriglyceridemic hamsters. Administration of AAV-hApoC2 via jugular or orbital vein in adult and neonatal ApoC2-deficient hamsters, respectively, could prevent the neonatal death and effectively improve severe hypertriglyceridemia of ApoC2-deficient hamsters without side effects in a long-term manner. Our novel findings in the present study demonstrate that AAV-hApoC2-mediated gene therapy will be a promising therapeutic approach for clinical patients with severe hypertriglyceridemia caused by ApoC2 deficiency.

• Authors: Chun Yang, Wenhong Tian, Sisi Ma, Mengmeng Guo, Xiao Lin, Fengying Gao, Xiaoyan Dong, Mingming Gao, Yuhui Wang, George Liu, Xunde Xian
• Journal: Molecular therapy. Methods & clinical development (Mol Ther Methods Clin Dev) Vol. 18 Pg. 692-701 (Sep 11 2020) ISSN: 2329-0501 [Print] United States
• PMID: 32802915 (Publication Type: Journal Article)
• Copyright: © 2020 The Author(s).