Gene therapy for Leber hereditary optic neuropathy.
Expert Opin Biol Ther
; 24(6): 521-528, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38939999
ABSTRACT
INTRODUCTION:
Leber hereditary optic neuropathy (LHON) is among the most frequent inherited mitochondrial disease, causing a severe visual impairment, mostly in young-adult males. The causative mtDNA variants (the three common are m.11778 G>A/MT-ND4, m.3460 G>A/MT-ND1, and m.14484T>C/MT-ND6) by affecting complex I impair oxidative phosphorylation in retinal ganglion cells, ultimately leading to irreversible cell death and consequent functional loss. The gene therapy based on allotopic expression of a wild-type transgene carried by adeno-associated viral vectors (AVV-based) appears a promising approach in mitochondrial disease and its efficacy has been explored in several large clinical trials. AREAS COVERED The review work employed basic concepts in mitochondrial diseases, LHON, and gene therapy procedures. Reports from completed trials in LHON (i.e. RESCUE) were reviewed and critically compared. EXPERT OPINION New challenges, as the improvement of the contralateral untreated eye or the apparently better outcome in patients treated in later stages (6-12 months), were highlighted by the latest gene therapy trials. A better understanding of the pathogenetic mechanisms of the disease together with combined therapy (medical and gene therapy) and optimization in genetic correction approaches could improve the visual outcome of treated eyes.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Atrofia Óptica Hereditaria de Leber
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Biol Ther
Asunto de la revista:
BIOLOGIA
/
TERAPEUTICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia