Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups.
Leber Hereditary Optic Neuropathy Gene Therapy: Adverse Events and Visual Acuity Results of All Patient Groups.
复制标题
DOI：
10.1016/j.ajo.2022.02.023
复制
发表时间：
2022-09
影响因子：
4.2
通讯作者：
Guy, John
中科院分区：
文献类型：
--
作者：
Lam, Byron L.;Feuer, William J.;Davis, Janet L.;Porciatti, Vittorio;Yu, Hong;Levy, Robert B.;Vanner, Elizabeth;Guy, John
目的：评价基因治疗G11778 A Leber遗传性视神经病变（LHON）的安全性。1期临床试验。单一机构。患有G11778 A LHON且慢性双侧视力丧失>12个月（组1，n=11）、急性双侧视力丧失<12个月（组2，n=9）或单侧视力丧失（组3，n=8）的患者。单侧玻璃体内AAV 2（Y 444，500，730 F）-P1 ND 4v 2注射，低、中、高和更高剂量注射至组1和2的较差眼和组3的较好眼。最佳矫正视力（BCVA）、不良事件和载体抗体应答。平均随访时间为24个月（范围12-36），将BCVA与已发表的具有指定替代研究和对侧眼的前瞻性自然病史队列进行比较。葡萄膜炎（8/28，29%）是唯一与载体相关的不良事件，不会导致可归因的视力后遗症，与载体剂量相关; 5/7（71%）高剂量眼睛与3/21（14%）低、中或高剂量眼睛（p<0.001）。需要治疗的葡萄膜炎事件与血清AAV 2中和抗体滴度增加相关（p=0.007），但与血清PCR无关。在第1组和第2组的一些治疗眼和对侧眼以及一些替代研究和自然病史受试者的对侧眼中，BCVA改善≥15字母。第3组中所有研究眼（BCVA ≥20/40）在第一年内丢失≥15个字母，尽管进行了治疗。G11778 A LHON基因治疗具有良好的安全性。我们的研究结果表明，如果有疗效，它可能很小，不与剂量相关。疗效的证明需要将患者随机分配至任一眼均未接受载体的组。在这项1期G11778 A LHON基因治疗临床试验中，发现了有利的安全性特征。葡萄膜炎是唯一与载体相关的不良事件，不会导致可归因的视力后遗症，并且与载体剂量相关。我们的研究结果表明，如果有疗效，它可能很小，不与剂量相关。疗效的证明需要将患者随机分配至任一眼均未接受载体的组。
To assess safety of gene therapy in G11778A Leber hereditary optic neuropathy (LHON). Phase 1 clinical trial. single institution. Patients with G11778A LHON and chronic bilateral visual loss >12 months (Group 1,n=11), acute bilateral visual loss <12 months (Group 2,n=9), or unilateral visual loss (Group 3,n=8). unilateral intravitreal AAV2(Y444,500,730F)-P1ND4v2 injection with low, medium, high and higher doses to worse eye for Groups 1 and 2 and better eye for Group 3. Best-corrected visual acuity (BCVA), adverse events, and vector antibody responses. Mean follow-up was 24 months (range 12–36), BCVAs were compared with a published prospective natural history cohort with designated surrogate study and fellow eyes. Incident uveitis (8/28,29%), the only vector-related adverse event, resulted in no attributable vision sequelae and was related to vector dose; 5/7(71%) higher-dose eyes versus 3/21(14%) low-, medium-, or high-dose eyes (p<0.001). Incident uveitis requiring treatment was associated with increased serum AAV2 neutralizing antibody titers (p=0.007) but not serum PCR. Improvements of ≥15 letter BCVA occurred in some treated and fellow eyes of Groups 1 and 2 and some surrogate study and fellow eyes of natural history subjects. All study eyes (BCVA ≥20/40) in Group 3 lost ≥15 letters within the first year despite treatment. G11778A LHON gene therapy has a favorable safety profile. Our results suggest if there is an efficacy effect, it is likely small and not dose-related. Demonstration of efficacy requires randomization of patients to a group not receiving vector in either eye. In this phase 1 G11778A LHON gene therapy clinical trial, a favorable safety profile was found. Incident uveitis was the only vector-related adverse event, resulted in no attributable vision sequelae and was related to vector dose. Our results suggest if there is an efficacy effect, it is likely small and not dose-related. Demonstration of efficacy requires randomization of patients to a group not receiving vector in either eye.
登录
查看更多内容
影响因子：
13.7
作者：
Feuer WJ;Schiffman JC;Davis JL;Porciatti V;Gonzalez P;Koilkonda RD;Yuan H;Lalwani A;Lam BL;Guy J
通讯作者：
Guy J
影响因子：
8.1
作者：
Lam, Byron L.;Feuer, William J.;Schiffman, Joyce C.;Porciatti, Vittorio;Vandenbroucke, Ruth;Rosa, Potyra R.;Gregori, Giovanni;Guy, John
通讯作者：
Guy, John
影响因子：
19
作者：
Glick, B;Wachter, C;Schatz, G
通讯作者：
Schatz, G
影响因子：
17.1
作者：
Yu-Wai-Man, Patrick;Newman, Nancy J.;Sahel, Jose-Alain
通讯作者：
Sahel, Jose-Alain
影响因子：
13.7
作者：
Newman, Nancy J.;Yu-Wai-Man, Patrick;Sahel, Jose-Alain
通讯作者：
Sahel, Jose-Alain