Gene Therapy for Retinal Diseases

Inherited retinal degenerations constitute a large and heterogeneous group of untreatable blinding conditions affecting 1 in 2000 people worldwide. They are caused by mutations in one of more than 200 genes mainly expressed in photoreceptor cells, as well as in the retinal pigment epithelium. Retinitis Pigmentosa (RP) and Stargardt disease (STGD1) are amongst the most frequent and severe forms of such retinal degenerative diseases.

The identification over the last three decades of genes implicated in retinal degeneration has laid the ground for the development of gene therapies to treat these types of diseases. Vectors derived from adeno-associated viruses (AAVs) are the ones of choice for retinal gene therapy due to their ability to efficiently target the different retinal layers. Furthermore, AAV vectors are safe, of low immunogenicity and enable long-term expression of the therapeutic gene following a single administration in patients. Indeed, the results of landmark phase I/II clinical trials of AAV-mediated gene therapy for type 2 Leber congenital amaurosis (a form of RP) constitute the first report of safe and effective gene addition in humans with severe degenerative diseases.

In its 15 years of existence, the Gene Therapy for Retinal Diseases team has accumulated a wealth of experience in translational research into gene therapies for inherited retinal dystrophies. Notably, the retina group has provided preclinical proof-of-concept for retinal gene therapy in canine models of RPE65 deficiency and of a rod-cone (PDE6ß-/-) and a cone-rod (RPGRIP1-/-) dystrophies. Importantly, the retina group in collaboration with the Ophtalmology department at the University Hospital in Nantes is the first in the world to develop an AAV4 vector for clinical trials and to successfully perform a Phase I/II trial for type 2 Leber congenital amaurosis with this vector (manuscript on preparation).

The group is currently focusing on the investigation of multiple approaches for the development of novel retinal gene therapies to treat retinitis pigmentosa and Stargardt disease, and on the generation of new animal models that more faithfully mimic the human condition in order to investigate disease mechanims and test the efficacy of potential gene therapies.


Team members: image.php

Carolina Isiegas (VMD, PhD, Group Leader )
Virginie Pichard (PhD)
Kizito-Tshitoko Tshilenge (PhD Student)
Baptiste Ameline (PhD Student)
Alexandra Mendes-Madeira (Technician)
Nathalie Provost (Technician)
Lyse Libeau (Orthoptiste)
Guylène Le Meur (PhD, Chef de clinique)
Michel Weber (Professeur)