近日，Spark Therapeutics公司的新型基因疗法Luxturna（voretigene neparvovec-rzyl）获美国FDA批用于治疗罹患一种遗传性视力丧失的儿童与成人患者，这种视力丧失可导致失明。Luxturna是美国批准的首个真正意义上的基因疗法，它的目标适应证是特定基因突变引起的一种疾病。
Luxturna通过向视网膜细胞直接输送一种正常拷贝的RPE65基因而发挥作用。这些视网膜细胞然后会产生正常的蛋白质，在视网膜上可以将光转化成一种电信号，从而恢复患者的视力丧失。Luxturna利用了一种自然产生的腺相关病毒，这种病毒已通过重组DNA技术得到改良，其作为一种载体向视网膜细胞输送正常的人 RPE65基因，从而使视力得到恢复。
批准日期：2017年12月21日 公司：Spark Therapeutics
LUXTURNA(voretigene neparvovec-rzyl)眼内悬液，为视网膜下注射眼内悬液
首次美国批准：2017
作用机理
LUXTURNA设计用于将编码人视网膜色素上皮65kDa蛋白（RPE65）的基因的正常拷贝传递给具有降低或缺乏生物活性RPE65水平的人的视网膜细胞。RPE65在视网膜色素上皮(RPE)细胞中产生，并将全反式视黄醇转化为11-顺-视黄醇，随后在视觉（视黄醇）周期中形成胆汁团，11-顺-视黄醇。视觉周期在光转导中至关重要，光转导是指光光子在视网膜电信号中的生物转化。RPE65基因突变导致RPE65水平降低或缺失异构水解酶活性，阻断视觉循环，导致视力损害。
适应症及用法
LUXTURNA是一种基于腺相关病毒载体的基因疗法，用于治疗确诊的双列RPE65突变相关视网膜营养不良患者。患者必须有由治疗医生确定的存活视网膜细胞。
剂量与给药
仅用于视网膜下注射。
●每只眼睛推荐剂量的LUXTURNA为1.5×1011载体基因组(vg)，通过视网膜下注射给药，总剂量为0.3mL。
●在间隔很近的时间内，但不少于6天，对每只眼睛分别进行LUXTURNA视网膜下给药。
·建议全身口服相当于泼尼松的皮质类固醇，每日1mg/kg(最多40mg/天)，共7天(从给每只眼睛施用LUXTURNA前3天开始)，并在随后的10天内逐渐减少。
剂型和强度
LUXTURNA是一种用于视网膜下注射的混悬液，以0.5mLextractable容量以单剂量2mL小瓶提供，用于单眼单次给药。供给的浓度(5x1012vg/mL)在施用前需要1:10稀释。稀释剂在两个单独使用的2-ML瓶中供应。
禁忌症
没有。
警告和注意事项
·眼内炎：使用适当的无菌注射技术，监测感染的体征和症状。
视力持续下降：监测视觉障碍。
●视网膜异常：监测黄斑异常、视网膜裂孔或破裂。切勿注射于黄斑中心附近。
●眼内压增加：监测和管理眼内压升高。
●眼内气泡的扩展：在吸收眼内气泡之前，不建议进行空中旅行和/或潜水。
·白内障：视网膜下注射LUXTURNA可导致白内障形成或白内障进展率增加。
不良反应
临床试验中最常见的不良反应（发生率≥5%）是结膜充血、白内障、眼压升高、视网膜病变、角膜基质变薄、黄斑裂孔、视网膜下沉积、眼部炎症、眼刺激、眼痛和黄斑病变（扭伤）。在黄斑的表面上。
在特定人群中的使用
儿科用途：不建议在12个月以下的婴儿中使用，因为该年龄组视网膜细胞增殖活跃，服用后LUXTURNA可能稀释或丢失。
包装供应/储存和搬运
每箱LUXTURNA(NDC 71394-415-01)含有一瓶单剂量LUXTURNA(NDC71394-065-01，0.5mL可提取体积)和两瓶稀释剂(NDC 71394-716-01，1.7mL)。每个小瓶中可提取的体积）。LUXTURNA每毫升含有5x1012载体基因组（vg），在给药前需要1：10稀释。
将LuxTurNA和稀释剂冷冻在65℃以下。
水瓶解冻后，存放在室温下。在室温下储存稀释的LuxurRNA [种子和给药]。
LuxTurRNA是一种基于腺相关病毒载体的基因治疗方法。遵循通用生物危害预防措施进行处理。

LUXTURNA(voretigene neparvovec-rzyl)intraocularsuspension for subretinal injection

LUXTURNA is a one-time gene therapy for individuals with an inherited retinal disease due to mutations in both copies of the RPE65 gene. Individuals must also have enough remaining cells in the retina.
INDICATION
LUXTURNA(voretigene neparvovec-rzyl)is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.
Patients must have viable retinal cells as determined by the treating physicians.
IMPORTANT SAFETY INFORMATION FOR LUXTURNA
Warnings and Precautions
Endophthalmitis may occur following any intraocular surgical procedure or injection. Use proper aseptic injection technique when administering LUXTURNA, and monitor for and advise patients to report any signs or symptoms of infection or inflammation to permit early treatment of any infection.
Permanent decline in visual acuity may occur following subretinal injection of LUXTURNA. Monitor patients for visual disturbances.
Retinal abnormalities may occur during or following the subretinal injection of LUXTURNA, including macular holes, foveal thinning, loss of foveal function, foveal dehiscence, and retinal hemorrhage. Monitor and manage these retinal abnormalities appropriately. Do not administer LUXTURNA in the immediate vicinity of the fovea. Retinal abnormalities may occur during or following vitrectomy, including retinal tears, epiretinal membrane, or retinal detachment. Monitor patients during and following the injection to permit early treatment of these retinal abnormalities. Advise patients to report any signs or symptoms of retinal tears and/or detachment without delay.
Increased intraocular pressure may occur after subretinal injection of LUXTURNA. Monitor and manage intraocular pressure appropriately.
Expansion of intraocular air bubbles Instruct patients to avoid air travel, travel to high elevations or scuba diving until the air bubble formed following administration of LUXTURNA has completely dissipated from the eye. It may take one week or more following injection for the air bubble to dissipate. A change in altitude while the air bubble is still present can result in irreversible vision loss. Verify the dissipation of the air bubble through ophthalmic examination.
Cataract Subretinal injection of LUXTURNA, especially vitrectomy surgery, is associated with an increased incidence of cataract development and/or progression.
Adverse Reactions
In clinical studies, ocular adverse reactions occurred in 66% of study participants (57% of injected eyes), and may have been related to LUXTURNA, the subretinal injection procedure, the concomitant use of corticosteroids, or a combination of these procedures and products.
The most common adverse reactions (incidence ≥5% of study participants) were conjunctival hyperemia (22%), cataract (20%), increased intraocular pressure (15%), retinal tear (10%), dellen (thinning of the corneal stroma) (7%), macular hole (7%), subretinal deposits (7%), eye inflammation (5%), eye irritation (5%), eye pain (5%), and maculopathy (wrinkling on the surface of the macula) (5%).
Immunogenicity
Immune reactions and extra-ocular exposure to LUXTURNA in clinical studies were mild. No clinically significant cytotoxic T-cell response to either AAV2 or RPE65 has been observed.
In clinical studies, the interval between the subretinal injections into the two eyes ranged from 7 to 14 days and 1.7 to 4.6 years. Study participants received systemic corticosteroids before and after subretinal injection of LUXTURNA to each eye, which may have decreased the potential immune reaction to either AAV2 or RPE65.
Pediatric Use
Treatment with LUXTURNA is not recommended for patients younger than 12 months of age, because the retinal cells are still undergoing cell proliferation, and LUXTURNA would potentially be diluted or lost during the cell proliferation. The safety and efficacy of LUXTURNA have been established in pediatric patients. There were no significant differences in safety between the different age subgroups.
1）：https://luxturna.com/#isi
2）：http://sparktx.com/LUXTURNA_US_Prescribing_Information.pdf