Gene Therapy with Voretigene Neparvovec Improves Vision and Partially Restores Electrophysiological Function in Pre-School Children with Leber Congenital Amaurosis.
Gene Therapy with Voretigene Neparvovec Improves Vision and Partially Restores Electrophysiological Function in Pre-School Children with Leber Congenital Amaurosis.
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Voretigene Neparvovec 基因治疗可改善患有 Leber 先天性黑蒙的学龄前儿童的视力并部分恢复电生理功能。
DOI：
10.3390/biomedicines11010103
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发表时间：
2022-12-30
期刊：
影响因子：
4.7
通讯作者：
Priglinger, Siegfried G.
中科院分区：
文献类型：
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作者：
Gerhardt, Maximilian J.;Priglinger, Claudia S.;Rudolph, Guenther;Hufendiek, Karsten;Framme, Carsten;Jaegle, Herbert;Salchow, Daniel J.;Anschuetz, Andreas;Michalakis, Stylianos;Priglinger, Siegfried G.
关键词：
由RPE65基因突变引起的Leber先天性黑朦属于最严重的早发遗传性儿童视网膜病变，自然发展为法定失明。新型基因疗法voretigene neparvovec是首个被批准用于这种毁灭性眼病的致病治疗方案，专门用于治疗rpe65介导的视网膜营养不良。在此，我们对迄今为止在德国接受治疗的最年轻患者进行了随访，包括4名学龄前儿童，他们在2020年1月至2022年5月期间在一个治疗中心接受了voretigene neparvovec治疗。所有患者均行玻璃体切割手术，注射部位内限定膜周向剥离，视网膜下注射voretigene neparvovec。术前和术后诊断包括影像学（光谱域光学相干断层扫描、眼底自身荧光、眼底广角成像）、电生理检查（ERG）、视网膜光敏度测量（FST）和视力测试。通过问卷调查和观察儿童在不同照明水平下的视觉引导行为来评估行为变化。在治疗后不久，所有儿童的视觉引导行为都有明显的提高，在术后过程中，视力也有明显的提高，其中一名儿童的视力达到了完全恢复。两只眼睛显示出治疗前无法检测到的ERG的部分电生理恢复——这一发现以前从未在人类身上被描述过。
Leber congenital amaurosis caused by mutations in the RPE65 gene belongs to the most severe early-onset hereditary childhood retinopathies naturally progressing to legal blindness. The novel gene therapy voretigene neparvovec is the first approved causative treatment option for this devastating eye disease and is specifically designed to treat RPE65-mediated retinal dystrophies. Herein, we present a follow-up of the youngest treated patients in Germany so far, including four pre-school children who received treatment with voretigene neparvovec at a single treatment center between January 2020 and May 2022. All patients underwent pars plana vitrectomy with circumferential peeling of the internal limiting membrane at the injection site and subretinal injection of voretigene neparvovec. Pre- and postoperative diagnostics included imaging (spectral domain optical coherence tomography, fundus autofluorescence, fundus wide-angle imaging), electrophysiologic examination (ERG), retinal light sensitivity measurements (FST) and visual acuity testing. Behavioral changes were assessed using a questionnaire and by observing the children’s vision-guided behavior in different levels of illumination. All children showed marked increase in vision-guided behavior shortly after therapy, as well as marked increase in visual acuity in the postoperative course up to full visual acuity in one child. Two eyes showed partial electrophysiological recovery of an ERG that was undetectable before treatment—a finding that has not been described in humans before.
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影响因子：
--
作者：
Jacobson, Samuel G.;Cideciyan, Artur V.;Ratnakaram, Ramakrishna;Heon, Elise;Schwartz, Sharon B.;Roman, Alejandro J.;Peden, Marc C.;Aleman, Tomas S.;Boye, Sanford L.;Sumaroka, Alexander;Conlon, Thomas J.;Calcedo, Roberto;Pang, Ji-Jing;Erger, Kirsten E.;Olivares, Melani B.;Mullins, Cristina L.;Swider, Malgorzata;Kaushal, Shalesh;Feuer, William J.;Iannaccone, Alessandro;Fishman, Gerald A.;Stone, Edwin M.;Byrne, Barry J.;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
13.7
作者：
Lorenz, B;Wabbels, B;Preising, MN
通讯作者：
Preising, MN
DOI：
10.1097/opx.0b013e31820846dd
发表时间：
2011-02
期刊：
Optometry and vision science : official publication of the American Academy of Optometry
影响因子：
--
作者：
Chung ST;LaFrance MW;Bedell HE
通讯作者：
Bedell HE
影响因子：
4.4
作者：
Lorenz, Birgit;Poliakov, Eugenia;Redmond, T. Michael
通讯作者：
Redmond, T. Michael
影响因子：
4.2
作者：
Chung, Daniel C.;Bertelsen, Mette;Reape, Kathleen Z.
通讯作者：
Reape, Kathleen Z.