From Bench to Bedside-Delivering Gene Therapy for Leber Hereditary Optic Neuropathy

Overview

Journal Cold Spring Harb Perspect Med

Specialty General Medicine

Date 2022 Jul 21

PMID 35863905

Authors

Benson S Chen

Patrick Yu-Wai-Man

Affiliations

Soon will be listed here.

Abstract

Leber hereditary optic neuropathy (LHON) is a rare, maternally inherited mitochondrial disorder that presents with severe bilateral sequential vision loss, due to the selective degeneration of retinal ganglion cells (RGCs). Since the mitochondrial genetic basis for LHON was uncovered in 1988, considerable progress has been made in understanding the pathogenetic mechanisms driving RGC loss, which has enabled the development of therapeutic approaches aimed at mitigating the underlying mitochondrial dysfunction. In this review, we explore the genetics of LHON, from bench to bedside, focusing on the pathogenetic mechanisms and how these have informed the development of different gene therapy approaches, in particular the technique of allotopic expression with adeno-associated viral vectors. Finally, we provide an overview of the recent gene therapy clinical trials and consider the unanswered questions, challenges, and future prospects.

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