Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy
In: Science Translational Medicine Science Translational Medicine, American Association for the Advancement of Science, 2020, 12 (573), ⟨10.1126/scitranslmed.aaz7423⟩ Science Translational Medicine, 2020, 12 (573), ⟨10.1126/scitranslmed.aaz7423⟩ Science translational medicine 12(573), eaaz7423 (2020). doi:10.1126/scitranslmed.aaz7423; (2020-12-09)
Online
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Zugriff:
International audience; REVERSE is a randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial that evaluated the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). A total of 37 subjects carrying the m.11778G>A (MT-ND4) mutation and with duration of vision loss between 6 to 12 months were treated. Each subject's right eye was randomly assigned in a 1:1 ratio to treatment with rAAV2/2-ND4 (GS010) or sham injection. The left eye received the treatment not allocated to the right eye. Unexpectedly, sustained visual improvement was observed in both eyes over the 96-week follow-up period. At week 96, rAAV2/2-ND4-treated eyes showed a mean improvement in best-corrected visual acuity (BCVA) of -0.308 LogMAR (+15 ETDRS letters). A mean improvement of -0.259 LogMAR (+13 ETDRS letters) was observed in the sham-treated eyes. Consequently, the primary end point, defined as the difference in the change in BCVA from baseline to week 48 between the two treatment groups, was not met (P = 0.894). At week 96, 25 subjects (68%) had a clinically relevant recovery in BCVA from baseline in at least one eye, and 29 subjects (78%) had an improvement in vision in both eyes. A nonhuman primate study was conducted to investigate this bilateral improvement. Evidence of transfer of viral vector DNA from the injected eye to the anterior segment, retina, and optic nerve of the contralateral noninjected eye supports a plausible mechanistic explanation for the unexpected bilateral improvement in visual function after unilateral injection.
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Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy
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| Autor/in / Beteiligte Person: | Rudolph, Günther ; Taiel, Magali ; Blouin, Laure ; Newman, Nancy J. ; Karanjia, Rustum ; Vignal-Clermont, Catherine ; Klopstock, Thomas ; Picaud, Serge ; Sergott, Robert C. ; Biousse, Valérie ; Smits, Gerard ; Chevalier, Caroline ; Moster, Mark L. ; Carelli, Valerio ; Chiara La Morgia ; Sadun, Alfredo A. ; Masonson, Harvey ; Yu-Wai-Man, Patrick ; Katz, Barrett ; Calkins, David J. ; Salermo, Yordak ; Burguière, Pierre ; Sahel, José-Alain ; University of Cambridge [UK] (CAM) ; Emory University School of Medicine ; Emory University [Atlanta, GA] ; University of Bologna ; Jefferson (Philadelphia University + Thomas Jefferson University) ; University of California [Los Angeles] (UCLA) ; University of California ; Munich Cluster for systems neurology [Munich] (SyNergy) ; Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU) ; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO) ; Fondation Ophtalmologique Adolphe de Rothschild [Paris] ; Ludwig Maximilian University [Munich] (LMU) ; University of Ottawa [Ottawa] ; Biologics, GenSight ; 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) ; Vanderbilt University Medical Center [Nashville] ; Vanderbilt University [Nashville] ; Institut Hospitalo-Universitaire FOReSIGHT ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU) ; University of Pittsburgh School of Medicine ; Pennsylvania Commonwealth System of Higher Education (PCSHE) ; HAL-SU, Gestionnaire ; University of Bologna/Università di Bologna ; University of California (UC) ; Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU) ; Centre d'investigation clinique Quinze-Vingts [CHNO] (CIC1423 - CIC QUINZE-VINGTS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) ; Yu-Wai-Man, P. ; N.J., Newman ; Carelli, V. ; M.L., Moster ; Biousse, V. ; A.A., Sadun ; Klopstock, T. ; Vignal-Clermont, C. ; R.C., Sergott ; Rudolph, G. ; la Morgia C. ; Karanjia, R. ; Taiel, M. ; Blouin, L. ; Burguiere, P. ; Smits, G. ; Chevalier, C. ; Masonson, H. ; Salermo, Y. ; Katz, B. ; Picaud, S. ; D.J., Calkins ; Sahel, J. A. ; Yu Wai Man, Patrick [0000-0001-7847-9320] ; Apollo - University of Cambridge Repository |
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| Quelle: | Science Translational Medicine Science Translational Medicine, American Association for the Advancement of Science, 2020, 12 (573), ⟨10.1126/scitranslmed.aaz7423⟩ Science Translational Medicine, 2020, 12 (573), ⟨10.1126/scitranslmed.aaz7423⟩ Science translational medicine 12(573), eaaz7423 (2020). doi:10.1126/scitranslmed.aaz7423; (2020-12-09) |
| Veröffentlichung: | HAL CCSD, 2020 |
| Medientyp: | unknown |
| ISSN: | 1946-6234 (print) ; 1946-6242 (print) |
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