Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy.

Humans Optic Atrophy, Hereditary, Leber / drug therapy Genetic Vectors Parvovirinae / genetics Genetic Therapy Inflammation / etiology
Intravitreal gene therapy Leber hereditary optic neuropathy Safety

Journal

American journal of ophthalmology
ISSN: 1879-1891
Titre abrégé: Am J Ophthalmol
Pays: United States
ID NLM: 0370500

Informations de publication

Date de publication:
05 2023
Historique:
received: 24 06 2022
revised: 04 11 2022
accepted: 29 11 2022
medline: 18 4 2023
pubmed: 11 12 2022
entrez: 10 12 2022
Statut: ppublish

Résumé

To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy. Pooled analysis of safety data from 5 clinical studies. A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2. Almost all patients (95.2%) received 9 × 10 Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.

Identifiants

DOI: 10.1016/j.ajo.2022.11.026 PMID: 36496192
pubmed: 36496192
pii: S0002-9394(22)00464-0
doi: 10.1016/j.ajo.2022.11.026
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108-125

Subventions

Organisme : Medical Research Council
ID : G0701386
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1002570
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS089694
Pays : United States
Organisme : Department of Health
ID : NIHR301696
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Auteurs

Catherine Vignal-Clermont (C)

From Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France (C.V-C.); Centre Hospitalier National d'Ophtalmologie des Quinze Vingts, Paris, France (C.V-C.). Electronic address: cvignal@for.paris.

Patrick Yu-Wai-Man (P)

Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK (P.Y-W-M.); Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK (P.Y-W-M.); UCL Institute of Ophthalmology, University College London, London, UK (P.Y-W-M.); Moorfields Eye Hospital, London, UK (P.Y-W-M.).

Nancy J Newman (NJ)

Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA (N.J.N. and V.B.).

Valerio Carelli (V)

IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy (V.C.); Unit of Neurology, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy (V.C.).

Mark L Moster (ML)

Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA (M.L.M., R.C.S.).

Valerie Biousse (V)

Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA (N.J.N. and V.B.).

Prem S Subramanian (PS)

Sue Anschutz-Rodgers University of Colorado Eye Center, University of Colorado School of Medicine, Aurora, CO, USA (P.S.S.).

An-Guor Wang (AG)

Department of Ophthalmology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan (A-G.W.).

Sean P Donahue (SP)

Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA (S.P.D.).

Bart P Leroy (BP)

Department of Ophthalmology and Center for Medical Genetics, Ghent University Hospital, and Department of Head & Skin, Ghent University, Ghent, Belgium (B.P.L.).

Alfredo A Sadun (AA)

Doheny Eye Institute, Los Angeles, CA, USA (A.A.S.); Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA (A.A.S.).

Thomas Klopstock (T)

Friedrich Baur Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany (T.K.); German Center for Neurodegenerative Diseases (DZNE), Munich, Germany (T.K.); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (T.K.).

Robert C Sergott (RC)

Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA (M.L.M., R.C.S.).

Gema Rebolleda Fernandez (G)

Department of Ophthalmology, Alcala University, Madrid, Spain (G.R.F.).

Bart K Chwalisz (BK)

Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA (B.K.C.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston MA, USA (B.K.C.).

Rudrani Banik (R)

Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA (R.B.).

Magali Taiel (M)

GenSight Biologics, Paris, France (M.T., M.R.).

Michel Roux (M)

GenSight Biologics, Paris, France (M.T., M.R.).

José-Alain Sahel (JA)

Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France (J-A.S.); Rothschild Foundation Hospital, Paris, France (J-A.S.); Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA (J-A.S.); Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Institut Hospitalo-Universitaire FOReSIGHT, INSERM-DGOS CIC, Paris, France (J-A.S.).

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Safety of Lenadogene Nolparvovec Gene Therapy...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Maladies mitochondriales › Atrophie optique héréditaire de Leber › Safety of Lenadogene Nolparvovec Gene Therapy...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Vecteurs génétiques › Safety of Lenadogene Nolparvovec Gene Therapy...
questionsmedicales.fr › Virus › Virus à ADN › Parvoviridae › Parvovirinae › Safety of Lenadogene Nolparvovec Gene Therapy...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Thérapie génétique › Safety of Lenadogene Nolparvovec Gene Therapy...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Safety of Lenadogene Nolparvovec Gene Therapy...