1 Lipid Clinic at the Interdisciplinary Metabolism Center, Charité-Universitätsmedizin Berlin , Berlin, Germany.
2 Medical Department, MD Medscript , Bad Dürkheim, Germany .
Hum Gene Ther. 2018 Apr;29(4):520-527. doi: 10.1089/hum.2018.007.
One-year results are reported of the first lipoprotein lipase deficiency (LPLD) patient treated with alipogene tiparvovec, which is indicated for the treatment of patients with genetically confirmed LPLD suffering from acute and recurrent pancreatitis attacks (PAs) despite dietary restrictions and expressing >5% of lipoprotein lipase (LPL) mass compared to a healthy control. During clinical development, alipogene tiparvovec has shown improvement of chylomicron metabolism and reduction of pancreatitis incidence up to 5.8 years post treatment. A 43-year-old female presented with severe hypertriglyceridemia (median triglyceride [TG] value of 3,465 mg/dL) and a history of 37 PAs within the last 25 years, despite treatment with fibrates, omega 3 fatty acids, and-since 2012-twice-weekly lipid apheresis. LPLD was confirmed by identification of two different pathogenic variants in the LPL gene located on separate alleles and therefore constituting a compound heterozygous state. With a detectable LPL mass level of 55.1 ng/mL, the patient was eligible for alipogene tiparvovec treatment, and in September 2015, she receved 40 injections (1 × 10 genome copies/kg) in the muscles of her upper legs under epidural anesthesia and immunosuppressive therapy. Alipogene tiparvovec was well tolerated: no injection site or systemic reactions were observed. Median TG values decreased by 52%, dropping to 997 mg/dL at month 3 and increasing thereafter. Within the first 18 months post treatment, the patient discontinued plasmapheresis and had no abdominal pain or PAs. In March 2017, the patient suffered from a PA due to diet violation. Within the first 12 months post treatment, overall quality of life improved, and no change in humoral or cellular immune response against LPL or AAV-1 was observed. In conclusion, alipogene tiparvovec was well tolerated, with a satisfactory response to treatment. Long-term effects on the recurrence of pancreatitis continue to be monitored.
报告了首例脂蛋白脂肪酶缺乏症（LPLD）患者接受脂肪酶基因定点整合腺相关病毒（AAV1）载体制剂（alipogene tiparvovec）治疗的一年结果。该药物用于治疗经基因确诊的脂蛋白脂肪酶缺乏症患者，这些患者尽管接受了饮食限制治疗，但仍反复发作急性胰腺炎（AP），且脂蛋白脂肪酶（LPL）质量相对于健康对照超过 5%。在临床开发中，alipogene tiparvovec 显示出改善乳糜微粒代谢的作用，并可将治疗后 5.8 年内胰腺炎的发作率降低 5.8 年。一位 43 岁的女性因严重的高甘油三酯血症（中位数甘油三酯 [TG] 值为 3465mg/dL）就诊，在过去 25 年内发生了 37 次 AP，尽管接受了贝特类药物、ω-3 脂肪酸和自 2012 年以来每周两次的血脂吸附治疗。通过在位于不同等位基因上的 LPL 基因中鉴定出两种不同的致病性变异，确认该患者患有 LPLD，因此构成复合杂合状态。由于可检测到 55.1ng/mL 的 LPL 质量水平，该患者符合 alipogene tiparvovec 治疗的条件，于 2015 年 9 月，在硬膜外麻醉和免疫抑制治疗下，在上大腿肌肉中接受了 40 次（1×10 个基因组拷贝/kg）注射。alipogene tiparvovec 耐受性良好：未观察到注射部位或全身反应。中位 TG 值下降 52%，从治疗后第 3 个月降至 997mg/dL，此后逐渐升高。在治疗后的前 18 个月内，该患者停止了血浆置换，未出现腹痛或 AP。2017 年 3 月，该患者因饮食不当而发生 AP。在治疗后的前 12 个月内，整体生活质量得到改善，未观察到针对 LPL 或 AAV1 的体液或细胞免疫反应发生变化。总之，alipogene tiparvovec 耐受性良好，治疗效果令人满意。继续监测对胰腺炎复发的长期影响。
