First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 gene
Purpose: to evaluate the results of gene therapy by the recombinant adeno-associated viral vector voretigene neparvovec (VN) in children with follow-up periods of 1, 3, 6, and 12 months.Material and methods. The study included 6 children (12 eyes) aged 5 to 15 with a confirmed biallelic mutation in...
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Real Time Ltd
2023-12-01
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| Series: | Российский офтальмологический журнал |
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| Online Access: | https://roj.igb.ru/jour/article/view/1356 |
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| author | V. V. Neroev L. A. Katargina M. P. Kharlampidi L. V. Kogoleva I. V. Zolnikova P. A. Ilyukhin E. V. Denisova S. V. Milash N. A. Osipova S. I. Kutsev A. V. Polyakov R. A. Zinchenko V. V. Kadyshev Yu. A. Bobrovskaya |
| author_facet | V. V. Neroev L. A. Katargina M. P. Kharlampidi L. V. Kogoleva I. V. Zolnikova P. A. Ilyukhin E. V. Denisova S. V. Milash N. A. Osipova S. I. Kutsev A. V. Polyakov R. A. Zinchenko V. V. Kadyshev Yu. A. Bobrovskaya |
| author_sort | V. V. Neroev |
| collection | DOAJ |
| description | Purpose: to evaluate the results of gene therapy by the recombinant adeno-associated viral vector voretigene neparvovec (VN) in children with follow-up periods of 1, 3, 6, and 12 months.Material and methods. The study included 6 children (12 eyes) aged 5 to 15 with a confirmed biallelic mutation in the RPE65 gene, treated with VN (Luxturna, USA). Treatment efficacy was assessed by surveying which included questions on spatial orientation under various types of illumination, Goldman perimetry, microperimetry, best corrected visual acuity (BCVA), electroretinogram (ERG), and visual evoked potentials (VEP). To assess the structure of the retina, the central retinal thickness (CRT) was evaluated by optical coherence tomography.Results. All children showed subjective changes in visual perception, including improved orientation in the dark and twilight, and improved contrast. In one case, the child with initially low visual acuity showed improved visual fixation. In 4 patients out of 6 (8 eyes), an expansion of the visual fields was noted, including 2 cases who displayed significant expansion thereof. In 2 patients (4 eyes), the visual fields were not narrowed and remained so throughout the entire observation period. Mean light sensitivity of the retina in 3 patients and fixation indices in 1 patient improved significantly as shown by microperimetry. BCVA remained stable throughout the study or changed insignificantly. Initially, ERG could not be detected in 8 eyes, but after an VN injection, 6 eyes demonstrated a partial recovery at different times — from 1 to 12 months. An increase in the amplitude of the P1 component to pattern VEP and P2 component to flash VEP was observed in all patients, which indicates an enhanced activity in the projection of the visual cortex after the restoration of the visual cycle. No significant changes were revealed in CRT (p = 0.9). Complications and adverse events were noted in 9 eyes (75 %): chorioretinal dystrophy at the injection site in 3 patients (5 eyes), multifocal nummular dystrophy in 2 patients (4 eyes), local episcleritis in 1 eye, transient increase in intraocular pressure in 2 patients (3 eyes).Conclusion. The results of a one-year post VN treatment follow-up of Russian patients with RPE65-associated inherited retinal disease demonstrate stabilization and improvement of visual functions, which is especially important for otherwise incurable patients with a progressive course of the disease. |
| format | Article |
| id | doaj-art-ad919c19fbe440018fc9394a33c70d4f |
| institution | Kabale University |
| issn | 2072-0076 2587-5760 |
| language | Russian |
| publishDate | 2023-12-01 |
| publisher | Real Time Ltd |
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| series | Российский офтальмологический журнал |
| spelling | doaj-art-ad919c19fbe440018fc9394a33c70d4f2025-08-20T03:39:28ZrusReal Time LtdРоссийский офтальмологический журнал2072-00762587-57602023-12-01164506210.21516/2072-0076-2023-16-4-50-62640First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 geneV. V. Neroev0L. A. Katargina1M. P. Kharlampidi2L. V. Kogoleva3I. V. Zolnikova4P. A. Ilyukhin5E. V. Denisova6S. V. Milash7N. A. Osipova8S. I. Kutsev9A. V. Polyakov10R. A. Zinchenko11V. V. Kadyshev12Yu. A. Bobrovskaya13Helmholtz National Medical Research Center of Eye Diseases; Evdokimov Moscow State University of Medicine and DentistryHelmholtz National Medical Research Center of Eye DiseasesHelmholtz National Medical Research Center of Eye DiseasesHelmholtz National Medical Research Center of Eye DiseasesHelmholtz National Medical Research Center of Eye Diseases; N.P. Bochkov Research Centre for Medical GeneticsHelmholtz National Medical Research Center of Eye DiseasesHelmholtz National Medical Research Center of Eye DiseasesHelmholtz National Medical Research Center of Eye DiseasesHelmholtz National Medical Research Center of Eye DiseasesN.P. Bochkov Research Centre for Medical GeneticsN.P. Bochkov Research Centre for Medical GeneticsN.P. Bochkov Research Centre for Medical GeneticsN.P. Bochkov Research Centre for Medical GeneticsHelmholtz National Medical Research Center of Eye DiseasesPurpose: to evaluate the results of gene therapy by the recombinant adeno-associated viral vector voretigene neparvovec (VN) in children with follow-up periods of 1, 3, 6, and 12 months.Material and methods. The study included 6 children (12 eyes) aged 5 to 15 with a confirmed biallelic mutation in the RPE65 gene, treated with VN (Luxturna, USA). Treatment efficacy was assessed by surveying which included questions on spatial orientation under various types of illumination, Goldman perimetry, microperimetry, best corrected visual acuity (BCVA), electroretinogram (ERG), and visual evoked potentials (VEP). To assess the structure of the retina, the central retinal thickness (CRT) was evaluated by optical coherence tomography.Results. All children showed subjective changes in visual perception, including improved orientation in the dark and twilight, and improved contrast. In one case, the child with initially low visual acuity showed improved visual fixation. In 4 patients out of 6 (8 eyes), an expansion of the visual fields was noted, including 2 cases who displayed significant expansion thereof. In 2 patients (4 eyes), the visual fields were not narrowed and remained so throughout the entire observation period. Mean light sensitivity of the retina in 3 patients and fixation indices in 1 patient improved significantly as shown by microperimetry. BCVA remained stable throughout the study or changed insignificantly. Initially, ERG could not be detected in 8 eyes, but after an VN injection, 6 eyes demonstrated a partial recovery at different times — from 1 to 12 months. An increase in the amplitude of the P1 component to pattern VEP and P2 component to flash VEP was observed in all patients, which indicates an enhanced activity in the projection of the visual cortex after the restoration of the visual cycle. No significant changes were revealed in CRT (p = 0.9). Complications and adverse events were noted in 9 eyes (75 %): chorioretinal dystrophy at the injection site in 3 patients (5 eyes), multifocal nummular dystrophy in 2 patients (4 eyes), local episcleritis in 1 eye, transient increase in intraocular pressure in 2 patients (3 eyes).Conclusion. The results of a one-year post VN treatment follow-up of Russian patients with RPE65-associated inherited retinal disease demonstrate stabilization and improvement of visual functions, which is especially important for otherwise incurable patients with a progressive course of the disease.https://roj.igb.ru/jour/article/view/1356inherited retinal dystrophiesgene therapyrpe65voretigen neparvovecluxturnaleber congenital amaurosisretinitis pigmentosagenetics, ophthalmology |
| spellingShingle | V. V. Neroev L. A. Katargina M. P. Kharlampidi L. V. Kogoleva I. V. Zolnikova P. A. Ilyukhin E. V. Denisova S. V. Milash N. A. Osipova S. I. Kutsev A. V. Polyakov R. A. Zinchenko V. V. Kadyshev Yu. A. Bobrovskaya First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 gene Российский офтальмологический журнал inherited retinal dystrophies gene therapy rpe65 voretigen neparvovec luxturna leber congenital amaurosis retinitis pigmentosa genetics, ophthalmology |
| title | First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 gene |
| title_full | First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 gene |
| title_fullStr | First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 gene |
| title_full_unstemmed | First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 gene |
| title_short | First results of long-term follow-up of children in Russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the RPE65 gene |
| title_sort | first results of long term follow up of children in russia after gene therapy for hereditary retinal dystrophies associated with biallelic mutations in the rpe65 gene |
| topic | inherited retinal dystrophies gene therapy rpe65 voretigen neparvovec luxturna leber congenital amaurosis retinitis pigmentosa genetics, ophthalmology |
| url | https://roj.igb.ru/jour/article/view/1356 |
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