Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study
| Autor: | Biousse, Valérie, Newman, Nancy J, Esposti, Simona, La Morgia, Chiara, Priglinger, Claudia, Karanja, Rustum, Blouin, Laure, Taiel, Magali, Sahel, José-Alain, Group, LHON Study, Yu-Wai-Man, Patrick, Carelli, Valerio, Moster, Mark L, Vignal-Clermont, Catherine, Klopstock, Thomas, Sadun, Alfredo A, Sergott, Robert C, Hage, Rabih |
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| Přispěvatelé: | Biousse V., Newman N.J., Yu-Wai-Man P., Carelli V., Moster M.L., Vignal-Clermont C., Klopstock T., Sadun A.A., Sergott R.C., Hage R., Esposti S., La Morgia C., Priglinger C., Karanja R., Blouin L., Taiel M., Sahel J.-A., Emory University School of Medicine, Emory University [Atlanta, GA], University College of London [London] (UCL), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Jefferson (Philadelphia University + Thomas Jefferson University), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Ludwig-Maximilians-Universität München (LMU), University of California [Los Angeles] (UCLA), University of California, National Institute for Health Research Moorfields Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, GenSight Biologics, Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Visual acuity Time Factors genetic structures Genetic enhancement Visual Acuity NADH dehydrogenase subunit 4 0302 clinical medicine Quality of life education.field_of_study metabolism [NADH Dehydrogenase] physiopathology [Optic Atrophy Hereditary Leber] Original Contribution Recombinant Protein Middle Aged genetics [DNA Mitochondrial] Recombinant Proteins Intravitreal Injections ComputingMethodologies_DOCUMENTANDTEXTPROCESSING [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Female medicine.symptom Tomography Optical Coherence Human Adult medicine.medical_specialty LEBER HEREDITARY OPTIC NEUROPATHY Composite score Time Factor Adolescent Long term follow up Population Optic Atrophy Hereditary Leber therapy [Optic Atrophy Hereditary Leber] DNA Mitochondrial Follow-Up Studie 03 medical and health sciences Young Adult methods [Genetic Therapy] Double-Blind Method Ophthalmology administration & dosage [Recombinant Proteins] medicine Humans ddc:610 [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs education Aged business.industry Intravitreal Injection NADH Dehydrogenase Genetic Therapy eye diseases Clinical trial genetics [Optic Atrophy Hereditary Leber] Mutation 030221 ophthalmology & optometry Quality of Life Neurology (clinical) Visual Fields genetics [NADH Dehydrogenase] business 030217 neurology & neurosurgery Follow-Up Studies |
| Zdroj: | Journal of Neuro-Ophthalmology Journal of Neuro-Ophthalmology, Lippincott, Williams & Wilkins, 2020, 41 (3), pp.309-315. ⟨10.1097/wno.0000000000001367⟩ Journal of neuro-ophthalmology 41(3), 309-315 (2021). doi:10.1097/WNO.0000000000001367 |
| ISSN: | 1536-5166 1070-8022 |
| DOI: | 10.1097/wno.0000000000001367⟩ |
| Popis: | Supplemental Digital Content is Available in the Text. Background: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials. Methods: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25). Results: The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline. Conclusion: The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss. |
| Databáze: | OpenAIRE |
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