ALIPOGENE TIPARVOVEC FOR THE TREATMENT OF LIPOPROTEIN LIPASE DEFICIENCY
ALIPOGENE TIPARVOVEC FOR THE TREATMENT OF LIPOPROTEIN LIPASE DEFICIENCY
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DOI：
10.1358/dot.2013.49.3.1937398
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发表时间：
2013-03-01
期刊：
影响因子：
1.8
通讯作者：
Haddley, K.
中科院分区：
文献类型：
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作者：
Haddley, K.
Alipo基因tiparvovec是首个被批准用于治疗代谢性疾病的腺相关病毒（AAV）介导的基因疗法。脂蛋白脂肪酶（LPL）缺乏症（LPLD）是一种罕见的常染色体隐性疾病，其基因突变导致血浆甘油三酯水解所需的催化活性酶的产生。由此产生的高甘油三酯血症会引起频繁的腹痛、皮肤和视网膜的脂肪沉积，并可能导致潜在的致命性胰腺炎。此外，LPLD患者可发展为糖尿病和心血管疾病。过去降低这些患者血浆甘油三酯的治疗无效。肌内注射脂肪基因替帕沃韦可将一种天然的功能获得性LPL基因变体LPLS447X传递到肌肉组织，并已在LPLD动物模型中证明了其有效性。在I/II期和临床评估中，脂源替帕沃韦可显著降低血浆甘油三酯和增加LPL活性，导致血浆乳糜微粒减少和胰腺炎发作频率降低。该疗法在动物和人类中耐受性良好，不会产生与治疗相关的严重不良反应。
Alipo gene tiparvovec is the first adeno-associated virus (AAV)-mediated gene therapy to be approved for the treatment of a metabolic disorder. Lipoprotein lipase (LPL) deficiency (LPLD) is a rare autosomal-recessive disorder in which gene mutations cause the production of a catalytically inactive enzyme required for plasma triglyceride hydrolysis. The resultant hypertriglyceridemia causes frequent abdominal pain, fatty deposits in the skin and retina, and can lead to potentially fatal pancreatitis. In addition, patients with LPLD can develop diabetes and cardiovascular disease. Past therapies to lower plasma triglycerides in these patients have been ineffective. Intramuscular injection of alipogene tiparvovec delivers a natural gain-of-function LPL gene variant, LPLS447X, to muscle tissue and has demonstrated efficacy in animal models of LPLD. In phase I/II and phase clinical evaluations, alipogene tiparvovec significantly lowered plasma triglycerides and increased LPL activity, resulting in a reduction in plasma chylomicron and a decrease in the frequency of pancreatitis episodes. The therapy is well tolerated in animals and humans and produces no serious treatment-related adverse effects.