Genersatztherapie bei hereditären Netzhauterkrankungen

Zusammenfassung

Charakteristisch für erblich bedingte Netzhauterkrankungen sind Funktionsausfälle in der Reizaufnahme und Reizweiterleitung innerhalb der Netzhaut, die zur Reduktion des Sehvermögens bis zur Blindheit führen. Dabei verursachen genetisch bedingte Ausfälle photorezeptorspezifischer Gene eine große Zahl von klinisch und ursächlich abgrenzbaren Krankheitsbildern, wobei jedes für sich zu den seltenen Erkrankungen gehört. In ihrer Gesamtheit und mit einer Prävalenz von 1 : 2500 sind die erblichen Netzhauterkrankungen jedoch ein klinisch bedeutsamer Erkrankungstypus – insbesondere auch im Hinblick auf die damit einhergehenden Einschränkungen in der Erwerbsfähigkeit und dem Verlust an Lebensqualität für die Betroffenen. Bis heute konnten Mutationen in über 250 Genen identifiziert werden, die für die verschiedenen Formen erblicher Netzhautdystrophien verantwortlich sind (https://sph.uth.tmc.edu/Retnet). Die präklinische Forschung an geeigneten Tiermodellen hat in den letzten Jahren große Fortschritte im Verständnis der Mutation zugrunde liegender pathologischer und molekularbiologischer Vorgänge ermöglicht. Basierend auf diesen Erkenntnissen haben sich neue Perspektiven für die Entwicklung innovativer Therapiestrategien für erbliche Netzhauterkrankungen beim Menschen eröffnet, welche weltweit bislang noch nicht heilbar sind. Der Erfolg präklinischer Studien hat zum Beginn mehrerer humaner Translationen geführt. Die Ergebnislage der laufenden humanen Studien macht jedoch auch die Notwendigkeit sichtbar, Optimierungsstrategien des neuen therapeutischen Ansatzes zu entwickeln und zu prüfen.

Abstract

Characteristics of inherited retinal dystrophies include deficiencies in light perception and nervous conduction within the retina, leading to reduced vision or even blindness. In this context, the loss of function of photoreceptor-specific genes causes a variety of clinically and aetiologically distinct syndromes – each of them belonging to the group of rare diseases. With a prevalence of 1 in 2500, however, inherited retinal diseases are clinically significant and important – especially since these diseases lead to restrictions of a patientʼs fitness for work and overall quality of life. More than 250 genetic mutations causing the various types of inherited retinal dystrophies have been identified by now (https://sph.uth.tmc.edu/Retnet). In recent years, preclinical research on suitable animal models has yielded important progress in the understanding of the mutations underlying the pathological and molecular biological processes of these diseases. These findings have led to the development of novel and innovative therapeutic strategies for the treatment of inherited retinal dysfunctions, which are still incurable. Meanwhile, many of the successful preclinical studies have led to translational research projects aiming to find treatment options for human patients. However, some preliminary results of these human translational studies indicate the need to optimise and refine the underlying therapeutic concepts.

Schlüsselwörter

erbliche Netzhauterkrankungen - rAAV-basierte Genersatztherapie - nicht invasive Diagnostikmethoden - CNG-Kanalprotein - Achromatopsie - Retinitis pigmentosa

Key words

non-invasive diagnostic methods - CNG channel proteins - achromatopsia - retinitis pigmentosa - hereditary retinal diseases - rAAV-mediated gene replacement therapy

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