Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset
In: Ophthalmology: Journal of The American Academy of Ophthalmology Ophthalmology: Journal of The American Academy of Ophthalmology, Elsevier, 2021, 128 (5), pp.649-660. ⟨10.1016/j.ophtha.2020.12.012⟩ Ophthalmology 128(5), 649-660 (2021). doi:10.1016/j.ophtha.2020.12.012; (2021-05-01)
Online
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Zugriff:
International audience; Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON).Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial.Participants: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included.Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye.Main outcome measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4-treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96.Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4-treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4-treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from -0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4-treated and sham-treated eyes was -0.01 logMAR (P = 0.89); the primary end point of a -0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4-treated and sham-treated eyes, respectively.Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes.
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Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset
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| Autor/in / Beteiligte Person: | Tsui, Irena ; Catarino, Claudia B. ; Barboni, Piero ; Rudolph, Günther ; Newman, Nancy J. ; Silvestri, Sara ; Sadun, Alfredo A. ; Dattilo, Michael ; Jurkute, Neringa ; Girmens, Jean-François ; Schertler, Cosima ; Taiel, Magali ; Karanjia, Rustum ; Priglinger, Claudia ; Maria K Gemenetzi ; Wolf, Armin ; Contin, Manuela ; Al-Tamami, Jasmina ; Klopstock, Thomas ; Acheson, James ; Sergott, Robert C. ; Gibbs, Deborah ; Hage, Rabih ; Thurau, Stephan R. ; DeBusk, Adam A. ; Lidia Di Vito ; Moster, Mark L. ; Biousse, Valérie ; Med Lindreth DuBois ; Carelli, Valerio ; Heilweil, Gad ; Chiara La Morgia ; Carbonelli, Michele ; Hendrick, Andrew ; Yu-Wai-Man, Patrick ; Peragallo, Jason H. ; Smits, Gerard ; Pressler, Angelika ; Hildebrandt, Martin ; Alcides Fernandes Filho ; Neuenhahn, Michael ; Bettina von Livonius ; Katz, Barrett ; Daniel R Muth ; Priglinger, Siegfried G. ; Leitch-Devlin, Lauren ; Mohamed, Susan ; Tucker, William R. ; Massini, Maria ; Eleftheriadou, Maria ; Blouin, Laure ; Vignal-Clermont, Catherine ; Hawy, Eman ; Simona Degli Esposti ; Tollis, Heather ; G. Baker Hubbard ; Jannah Rutter Dobbs ; Sahel, José-Alain ; Vignal, Catherine ; SantaMaria, Melissa ; Haller, Julie A. ; Emory University School of Medicine ; Emory University [Atlanta, GA] ; Hospital, Addenbrooke's ; Cambridge University NHS Trust ; Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) ; University of Bologna ; Jefferson (Philadelphia University + Thomas Jefferson University) ; Fondation Ophtalmologique Adolphe de Rothschild [Paris] ; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO) ; Ludwig-Maximilians-Universität München (LMU) ; University of California [Los Angeles] (UCLA) ; University of California ; Ludwig Maximilian University [Munich] (LMU) ; 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) ; University of Pittsburgh School of Medicine ; Pennsylvania Commonwealth System of Higher Education (PCSHE) ; 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) ; Newman, NJ ; Yu-Wai-Man, P ; Carelli, V ; Moster, ML ; Biousse, V ; Vignal-Clermont, C ; Sergott, RC ; Klopstock, T ; Sadun, AA ; Barboni, P ; DeBusk, AA ; Girmens, JF ; Rudolph, G ; Karanjia, R ; Taiel, M ; Blouin, L ; Smits, G ; Katz, B ; Sahel, J-A ; Vignal, C ; Hage, R ; Catarino, CB ; Priglinger, C ; Priglinger, S ; Thurau, S ; von Livonius, B ; Muth, D ; Wolf, A ; Al-Tamami, J ; Pressler, A ; Schertler, C ; Hildebrandt, M ; Neuenhahn, M ; Heilweil, G ; Tsui, I ; Hubbard, GB ; Hendrick, A ; Dattilo, M ; Peragallo, J ; Hawy, E ; DuBois, Med L ; Gibbs, D ; Filho, AF ; Dobbs, J ; Carbonelli, M ; Di Vito, L ; Contin, M ; Mohamed, S ; La Morgia, C ; Silvestri, S ; Acheson, J ; Eleftheriadou, M ; Esposti, S ; Gemenetzi, M ; Leitch-Devlin, L ; Tucker, WR ; Jurkute, N ; SantaMaria, M ; Tollis, H ; Haller, JA ; Massini, M. |
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| Quelle: | Ophthalmology: Journal of The American Academy of Ophthalmology Ophthalmology: Journal of The American Academy of Ophthalmology, Elsevier, 2021, 128 (5), pp.649-660. ⟨10.1016/j.ophtha.2020.12.012⟩ Ophthalmology 128(5), 649-660 (2021). doi:10.1016/j.ophtha.2020.12.012; (2021-05-01) |
| Veröffentlichung: | HAL CCSD, 2021 |
| Medientyp: | unknown |
| ISSN: | 0161-6420 (print) |
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