Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jan;81(1):57-86.
doi: 10.1007/s40265-020-01428-3.

Therapeutic Options in Hereditary Optic Neuropathies

Giulia Amore  1 , Martina Romagnoli  2 , Michele Carbonelli  2 , Piero Barboni  3 , Valerio Carelli  1   2 , Chiara La Morgia  4
Affiliations
Review

Therapeutic Options in Hereditary Optic Neuropathies

Giulia Amore et al. Drugs. 2021 Jan.

Abstract

Options for the effective treatment of hereditary optic neuropathies have been a long time coming. The successful launch of the antioxidant idebenone for Leber's Hereditary Optic Neuropathy (LHON), followed by its introduction into clinical practice across Europe, was an important step forward. Nevertheless, other options, especially for a variety of mitochondrial optic neuropathies such as dominant optic atrophy (DOA), are needed, and a number of pharmaceutical agents, acting on different molecular pathways, are currently under development. These include gene therapy, which has reached Phase III development for LHON, but is expected to be developed also for DOA, whilst most of the other agents (other antioxidants, anti-apoptotic drugs, activators of mitobiogenesis, etc.) are almost all at Phase II or at preclinical stage of research. Here, we review proposed target mechanisms, preclinical evidence, available clinical trials with primary endpoints and results, of a wide range of tested molecules, to give an overview of the field, also providing the landscape of future scenarios, including gene therapy, gene editing, and reproductive options to prevent transmission of mitochondrial DNA mutations.

PubMed Disclaimer

Conflict of interest statement

VC acts as scientific consultant in boards of GenSight Biologics, Stealth BioTherapeutics, Santhera Pharmaceuticals, and Chiesi. VC received speaker honoraria from Chiesi and an unrestricted research grant from Stealth BioTherapeutics. PB, MC, VC, CLM, MR, received speaker’s honoraria and travel support from Santhera Pharmaceuticals. PB received speaker honoraria from GenSight Biologics, Visufarma and Omkron. CLM received consulting fees from Regulatory Pharmanet and Chiesi Pharmaceuticals. GA, PB, MC, VC, CLM are investigators in clinical trials from Santhera Pharmaceuticals and GenSight Biologics. MR serves as Study Coordinator in Santhera Pharmaceuticals and GenSight Biologics sponsored trials. None of these activities are in any way related to the writing of this study.

Figures

Fig. 1
Fig. 1
Therapeutic strategies in Leber's Hereditary Optic Neuropathy (LHON). This figure schematically shows the mechanism of action for the different therapeutic approaches in Hereditary Optic Neuropathies
See this image and copyright information in PMC

References

    1. Carelli V, Ross-Cisneros FN, Sadun AA. Mitochondrial dysfunction as a cause of optic neuropathies. Prog Retin Eye Res. 2004;23(1):53–89. - PubMed
    1. Yu-Wai-Man P, Griffiths PG, Chinnery PF. Mitochondrial optic neuropathies—disease mechanisms and therapeutic strategies. Prog Retin Eye Res. 2011;30(2):81–114. - PMC - PubMed
    1. La Morgia C, Carbonelli M, Barboni P, Sadun AA, Carelli V. Medical management of hereditary optic neuropathies. Front Neurol. 2014;5:141. - PMC - PubMed
    1. Achilli A, Iommarini L, Olivieri A, Pala M, Hooshiar Kashani B, Reynier P, La Morgia C, Valentino ML, Liguori R, Pizza F, Barboni P, et al. Rare primary mitochondrial DNA mutations and probable synergistic variants in Leber's hereditary optic neuropathy. PLoS ONE. 2012;7(8):e42242. - PMC - PubMed
    1. Del Dotto V, Fogazza M, Carelli V, Rugolo M, Zanna C. Eight human opa1 isoforms, long and short: What are they for? Biochim Biophys Acta Bioenergy. 2018;1859(4):263–269. - PubMed

MeSH terms

LinkOut - more resources