Jacobson Samuel G, Cideciyan Artur V, Ho Allen C, Peshenko Igor V, Garafalo Alexandra V, Roman Alejandro J, Sumaroka Alexander, Wu Vivian, Krishnan Arun K, Sheplock Rebecca, Boye Sanford L, Cheang Bee-Lin, Davidson Vanessa, O'Riordan Catherine R, Dizhoor Alexander M, Boye Shannon E
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.
iScience. 2021 Apr 11;24(5):102409. doi: 10.1016/j.isci.2021.102409. eCollection 2021 May 21.
A first-in-human clinical trial of gene therapy in Leber congenital amaurosis due to mutations in the gene is underway, and early results are summarized. A recombinant adeno-associated virus serotype 5 (rAAV5) vector carrying the human gene was delivered by subretinal injection to one eye in three adult patients with severe visual loss, nystagmus, but preserved retinal structure. Safety and efficacy parameters were monitored for 9 months post-operatively. No systemic toxicity was detected; there were no serious adverse events, and ocular adverse events resolved. P1 and P2 showed statistically significant rod photoreceptor vision improvement by full-field stimulus testing in the treated eye. P1 also showed improvement in pupillary responses. Visual acuity remained stable from baseline in P1 and P2. P3, however, showed a gain of 0.3 logMAR in the treated eye, indicating greater cone-photoreceptor function. The results show safety and both rod- and cone-mediated efficacy of this therapy.
一项针对因该基因突变导致的莱伯先天性黑蒙的基因治疗首次人体临床试验正在进行，并总结了早期结果。携带人类基因的重组腺相关病毒5型（rAAV5）载体通过视网膜下注射递送至三名严重视力丧失、眼球震颤但视网膜结构保留的成年患者的一只眼睛。术后9个月监测安全性和疗效参数。未检测到全身毒性；未发生严重不良事件，眼部不良事件已解决。通过全视野刺激测试，P1和P2在治疗眼的视杆光感受器视力改善方面具有统计学意义。P1的瞳孔反应也有所改善。P1和P2的视力与基线相比保持稳定。然而，P3治疗眼的最小分辨角对数视力提高了0.3，表明视锥光感受器功能增强。结果显示了该疗法的安全性以及视杆和视锥介导的疗效。
