Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial.
Mitochondrial disorders cannot be ignored anymore in most medical disciplines; indeed their minimum estimated prevalence is superior to 1 in 5000 births. Despite the progress made in the last 25 years on the identification of gene mutations causing mitochondrial pathologies, only slow progress was made towards their effective treatments. Ocular involvement is a frequent feature in mitochondrial diseases and corresponds to severe and irreversible visual handicap due to retinal neuron loss and optic atrophy. Interestingly, three clinical trials for Leber Congenital Amaurosis due to RPE65 mutations are ongoing since 2007. Overall, the feasibility and safety of ocular Adeno-Associated Virus delivery in adult and younger patients and consistent visual function improvements have been demonstrated. The success of gene-replacement therapy for RPE65 opens the way for the development of similar approaches for a broad range of eye disorders, including those with mitochondrial etiology such as Leber Hereditary Optic Neuropathy (LHON).
INSERM, U968, Paris 75012, France; Sorbonne Universités, UPMC université Paris 6, UMR_S 968, Institut de la vision, Paris 75012, France; CNRS, UMR_7210, Paris 75012, France.
Hélène
H
Cwerman-Thibault
INSERM, U968, Paris 75012, France; Sorbonne Universités, UPMC université Paris 6, UMR_S 968, Institut de la vision, Paris 75012, France; CNRS, UMR_7210, Paris 75012, France.
Sébastien
S
Augustin
INSERM, U968, Paris 75012, France; Sorbonne Universités, UPMC université Paris 6, UMR_S 968, Institut de la vision, Paris 75012, France; CNRS, UMR_7210, Paris 75012, France.
Sami
S
Ellouze
INSERM, U968, Paris 75012, France; Sorbonne Universités, UPMC université Paris 6, UMR_S 968, Institut de la vision, Paris 75012, France; CNRS, UMR_7210, Paris 75012, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, 75012 Paris, France; Fondation Ophtalmologique Adolphe-de-Rothschild, 75019 Paris, France; Institute of Ophthalmology, University College of London, London EC1V 9EL, UK; French Academy of Sciences, Institut de France, 75006 Paris, France.
José-Alain
JA
Sahel
INSERM, U968, Paris 75012, France; Sorbonne Universités, UPMC université Paris 6, UMR_S 968, Institut de la vision, Paris 75012, France; CNRS, UMR_7210, Paris 75012, France. Electronic address: marisol.corral@inserm.fr.
Marisol
M
Corral-Debrinski
D002986:Clinical Trials as Topic; D005128:Eye Diseases / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics / Q000628:therapy*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000628:therapy*
AAV vectors; Chaîne respiratoire; Gene therapy; LHON; Mitochondria; Mitochondrie; NOHL; Nerf optique; Optic nerve; Respiratory chain; Retina; Rétine; Thérapie génique; Vecteur AAV