[Gene therapy in ophthalmology].
Gentherapie in der Augenheilkunde.
Age-related macular degeneration
Gene delivery systems
Leber’s hereditary optic neuropathy
RPE65
Voretigene neparvovec-rzyl
Journal
Die Ophthalmologie
ISSN: 2731-7218
Titre abrégé: Ophthalmologie
Pays: Germany
ID NLM: 9918402288106676
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
accepted:
25
05
2023
medline:
9
8
2023
pubmed:
7
7
2023
entrez:
7
7
2023
Statut:
ppublish
Résumé
In 2017 the gene therapy medication voretigene neparvovec-rzyl was approved by the U.S. Food and Drug Administration (FDA) for retinal gene therapy of hereditary retinal dystrophies caused by mutations in the RPE65 gene. Voretigene neparvovec-rzyl is a gene augmentation therapy using an adeno-associated virus-based vector to express a healthy copy of the human RPE65 gene in the patient's retinal pigment epithelial (RPE) cells. The success of gene augmentation therapy in RPE65-linked retinal dystrophy encouraged research activities on the concept of gene supplementation to be extended to nongenetic diseases, such as age-related macular degeneration; however, it also showed that the principle of success cannot be easily extended to other retinal dystrophies. This review article presents the most commonly used principles and technologies of gene therapy and provides an overview of the current challenges and limitations. Furthermore, practice-relevant aspects of the indications and the treatment procedure are discussed. Particular attention is paid to the consideration of disease stages, especially with respect to patient's expectations and the evaluation of treatment success. Im Jahr 2017 wurde das Gentherapeutikum Voretigene neparvovec-rzyl zur Behandlung von durch Mutationen im Gen RPE65 verursachten hereditären Netzhautdystrophien zugelassen. Es handelt sich dabei um eine Genaugmentationstherapie, bei der ein Vektor auf Basis von adenoassoziierten Viren verwendet wird, um eine gesunde Kopie des menschlichen RPE65-Gens in den retinalen Pigmentepithelzellen des Betroffenen zu exprimieren. Der Erfolg der Genaugmentationstherapie für die RPE65-gebundene Netzhautdystrophie trug einerseits dazu bei, die Forschungsaktivitäten zum Konzept der Gensupplementierung auch auf nichtgenetische Erkrankungen wie die altersbedingte Makuladegeneration auszuweiten, andererseits zeigte sich aber auch, dass sich das Erfolgsprinzip nicht ohne Weiteres auf andere Netzhautdystrophien ausweiten lässt. Diese Übersicht soll die wichtigsten Prinzipien und Technologien vorstellen und einen Überblick über deren Herausforderungen und Grenzen geben. Darüber hinaus werden praxisrelevante Aspekte bei Indikationsstellung und Therapie erörtert. Besonderes Augenmerk gebührt der Berücksichtigung der Krankheitsstadien, insbesondere im Hinblick auf die Erwartungen der Betroffenen und die Bewertung der Therapieerfolge.
Autres résumés
Type: Publisher
(ger)
Im Jahr 2017 wurde das Gentherapeutikum Voretigene neparvovec-rzyl zur Behandlung von durch Mutationen im Gen RPE65 verursachten hereditären Netzhautdystrophien zugelassen. Es handelt sich dabei um eine Genaugmentationstherapie, bei der ein Vektor auf Basis von adenoassoziierten Viren verwendet wird, um eine gesunde Kopie des menschlichen RPE65-Gens in den retinalen Pigmentepithelzellen des Betroffenen zu exprimieren. Der Erfolg der Genaugmentationstherapie für die RPE65-gebundene Netzhautdystrophie trug einerseits dazu bei, die Forschungsaktivitäten zum Konzept der Gensupplementierung auch auf nichtgenetische Erkrankungen wie die altersbedingte Makuladegeneration auszuweiten, andererseits zeigte sich aber auch, dass sich das Erfolgsprinzip nicht ohne Weiteres auf andere Netzhautdystrophien ausweiten lässt. Diese Übersicht soll die wichtigsten Prinzipien und Technologien vorstellen und einen Überblick über deren Herausforderungen und Grenzen geben. Darüber hinaus werden praxisrelevante Aspekte bei Indikationsstellung und Therapie erörtert. Besonderes Augenmerk gebührt der Berücksichtigung der Krankheitsstadien, insbesondere im Hinblick auf die Erwartungen der Betroffenen und die Bewertung der Therapieerfolge.
Identifiants
pubmed: 37418021
doi: 10.1007/s00347-023-01883-9
pii: 10.1007/s00347-023-01883-9
doi:
Types de publication
Review
English Abstract
Journal Article
Langues
ger
Sous-ensembles de citation
IM
Pagination
867-882Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
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