학술논문
Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.
Document Type
Academic Journal
Author
Yu-Wai-Man P; John van Geest Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UK; MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK; Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK; Institute of Ophthalmology, University College London, London EC1V 9EL, UK.; Carelli V; IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, 40139 Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, 40127 Bologna, Italy.; Newman NJ; Departments of Ophthalmology, Neurology, and Neurological Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.; Silva MJ; All is Data, 4052 Basel, Switzerland.; Linden A; EstiMates Oy, 20520 Turku, Finland.; Van Stavern G; Washington University in St. Louis, St. Louis, MO 63130, USA.; Szaflik JP; Department of Ophthalmology, Medical University of Warsaw, 02-091 Warsaw, Poland; SPKSO Ophthalmic University Hospital, 00-576 Warsaw, Poland.; Banik R; New York Eye and Ear Infirmary of Mount Sinai, New York, NY 10003, USA.; Lubiński W; Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie, 70-111 Szczecin, Poland.; Pemp B; Department of Ophthalmology, Medical University of Vienna, 1090 Vienna, Austria.; Liao YJ; Stanford University Byers Eye Institute, Palo Alto, CA 94303, USA.; Subramanian PS; Sue Anschutz-Rodgers University of Colorado Eye Center, Aurora, CO 80045, USA.; Misiuk-Hojło M; Wrocław Medical University, 50-556 Wrocław, Poland.; Newman S; University of Virginia, Charlottesville, VA 22903, USA.; Castillo L; Institut Catala de Retina (ICR), 08022 Barcelona, Spain.; Kocięcki J; Department of Ophthalmology, University of Medical Sciences, 60-806 Poznan, Poland.; Levin MH; Department of Ophthalmology, Palo Alto Medical Foundation, Palo Alto, CA 94303, USA.; Muñoz-Negrete FJ; Hospital Universitario Ramon y Cajal, IRYCIS, Universidad Alcalá, 28034 Madrid, Spain.; Yagan A; Manchester Royal Eye Hospital, Manchester M13 9WL, UK.; Cherninkova S; UMHAT 'Alexandrovska' EAD, 1431 Sofia, Bulgaria.; Katz D; Bethesda Neurology LLC, Bethesda, MD 20852, USA.; Meunier A; Department of Ophthalmology, CHU Saint-Pierre, 1000 Brussels, Belgium.; Votruba M; Cardiff Eye Unit, University Hospital of Wales, Cardiff CF14 4XW, UK.; Korwin M; Department of Ophthalmology, Medical University of Warsaw, 02-091 Warsaw, Poland; SPKSO Ophthalmic University Hospital, 00-576 Warsaw, Poland.; Dziedziak J; Department of Ophthalmology, Medical University of Warsaw, 02-091 Warsaw, Poland; SPKSO Ophthalmic University Hospital, 00-576 Warsaw, Poland; Department of Experimental and Clinical Physiology, Center for Preclinical Research, Medical University of Warsaw, 02-097 Warsaw, Poland.; Jurkutė N; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK; Institute of Ophthalmology, University College London, London EC1V 9EL, UK; The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London WC1N 3BG, UK.; Harvey JP; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK; Institute of Ophthalmology, University College London, London EC1V 9EL, UK.; La Morgia C; IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, 40139 Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, 40127 Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.; Priglinger C; Department of Ophthalmology, University Hospital of the Ludwig-Maximilians-University (LMU), 80336 Munich, Germany.; Llòria X; Chiesi Farmaceutici S.p.A., 43100 Parma, Italy.; Tomasso L; Chiesi Farmaceutici S.p.A., 43100 Parma, Italy.; Klopstock T; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany; Friedrich Baur Institute at the Department of Neurology, LMU University Hospital, LMU Munich, 80336 Munich, Germany. Electronic address: thomas.klopstock@med.uni-muenchen.de.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
Subject
Language
English
Abstract
Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.
Competing Interests: Declaration of interests P.Y.-W.-M., V.C., N.J.N., B.P., L.C., and T.K. received research support and/or personal compensation from Santhera Pharmaceuticals, Chiesi, and GenSight Biologics. P.Y.-W.-M. is also a consultant for Neurophth and Stoke Therapeutics. N.J.N. is also a consultant for Santhera Pharmaceutical, Chiesi, GenSight Biologics, Stoke Therapeutics, Avidity Biosciences, and Neurophoenix SAS, and has been a speaker and contributing writer for educational activities under the auspices of WebMD and First Class. P.S.S. is a consultant to GenSight Biologics and received research support from GenSight Biologics and Santhera Pharmaceuticals. M.H.L. received personal compensation from Santhera Pharmaceuticals. C.L.M. has acted as a consultant for Chiesi Farmaceutici, Regulatory PharmaNet, and Thenewway srl, and has also received speaker honoraria and/or financial support for meetings from these companies, as well as from First Class srl and Biologix. C.L.M. has also acted as a principal or study investigator for clinical trials sponsored by GenSight Biologics, Santhera Pharmaceuticals, Stoke Therapeutics, and Reneo Pharmaceuticals. C.P. received personal compensation from Novartis and has acted as an investigator in clinical trials for Santhera Pharmaceuticals, GenSight Biologics, and Iveric Bio. X.L. and L.T. are employees of Chiesi Farmaceutici S.p.A.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests P.Y.-W.-M., V.C., N.J.N., B.P., L.C., and T.K. received research support and/or personal compensation from Santhera Pharmaceuticals, Chiesi, and GenSight Biologics. P.Y.-W.-M. is also a consultant for Neurophth and Stoke Therapeutics. N.J.N. is also a consultant for Santhera Pharmaceutical, Chiesi, GenSight Biologics, Stoke Therapeutics, Avidity Biosciences, and Neurophoenix SAS, and has been a speaker and contributing writer for educational activities under the auspices of WebMD and First Class. P.S.S. is a consultant to GenSight Biologics and received research support from GenSight Biologics and Santhera Pharmaceuticals. M.H.L. received personal compensation from Santhera Pharmaceuticals. C.L.M. has acted as a consultant for Chiesi Farmaceutici, Regulatory PharmaNet, and Thenewway srl, and has also received speaker honoraria and/or financial support for meetings from these companies, as well as from First Class srl and Biologix. C.L.M. has also acted as a principal or study investigator for clinical trials sponsored by GenSight Biologics, Santhera Pharmaceuticals, Stoke Therapeutics, and Reneo Pharmaceuticals. C.P. received personal compensation from Novartis and has acted as an investigator in clinical trials for Santhera Pharmaceuticals, GenSight Biologics, and Iveric Bio. X.L. and L.T. are employees of Chiesi Farmaceutici S.p.A.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)