Leber Hereditary Optic Neuropathy (LHON)
Leber hereditary optic neuropathy (LHON) is an optic mitochondrial disorder which causes sharp or gradual loss of both eyesight due to the degeneration of the retinal ganglion cells. Protheragen has highly skilled experts in LHON, which enables them to understand the disorder profoundly. They are dedicated to developing innovative therapies that are aimed for LHON, hoping to fill the existing gaps in treatment options and further the progression of precision medicine in this area.
Introduction to Leber Hereditary Optic Neuropathy (LHON)
Leber hereditary optic neuropathy (LHON) is an inherited genetic neurodegenerative disorder, as it typically is, with an affected individual experiencing bilateral vision loss due to the degeneration of retinal ganglion cells (RGCs) and consequent optic atrophy. It is associated with pathogenic changes in the mitochondrial DNA (mtDNA) paradigm, due to mutations in the genes which code for the subunit of complex I of the electron transport chain (ETC) system.
Fig.1 The diagram represents the electron transport chain and the three common primary mutations at mitochondrial nucleotide positions 3460, 11,778, and 14,484. (Chi S C, et al., 2022)
Pathogenesis of Leber Hereditary Optic Neuropathy (LHON)
Leber hereditary optic neuropathy (LHON) is primarily associated with mutations in mitochondrial DNA (m.3460G>A/MT-ND1, m.11778G>A/MT-ND4, m.14484T>C/MT-ND6) which cause impotence of complex I and oxidative phosphorylation, over-production of reactive oxygen species, and, in the end, energy depletion-induced apoptosis of retinal ganglion cells. Men express the disease more than women because of some genetic and environmental factors.
Fig.2 Treatment strategies for Leber hereditary optic neuropathy (LHON). (Zhou Q, et al., 2024)
Therapeutic Development for Leber Hereditary Optic Neuropathy (LHON)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| rAAV2-ND4 | Recombinant AAV2 vector delivering wild-type human MT-ND4 gene | Mutant mitochondrial complex I | NCT01267422 | Phase III |
| GS010 | Gene therapy restoring functional ND4 subunit of mitochondrial complex I | MT-ND4 gene | NCT03293524 | Phase III |
| EPI-743 | Synthetic benzoquinone that enhances mitochondrial electron transport and reduces oxidative stress | Mitochondrial complex I/III | NCT02300753 | Phase II/III |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
As a preclinical research service provider for Leber hereditary optic neuropathy (LHON), Protheragen provides end-to-end diagnostic and therapeutic development solutions. We excel in building physiologically relevant models, including in vitro models, animal models, and specialized blood-brain barrier (BBB) models, to enable comprehensive biomarker discovery, target validation, and CNS drug efficacy optimization.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- ND6 P25L Mutation Model: a genetically engineered mouse model that recapitulates LHON-associated complex I dysfunction and selective retinal ganglion cell degeneration.
- Rotenone-induced Model: Induces mitochondrial dysfunction and oxidative stress in retinal neurons.
Protheragen is steadfastly dedicated to meticulously validating and optimizing therapies for Leber hereditary optic neuropathy (LHON) through a thorough series of pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Chi S C, Cheng H C, Wang A G. Leber hereditary optic neuropathy: molecular pathophysiology and updates on gene therapy[J]. Biomedicines, 2022, 10(8): 1930.
- Zhou Q, Liu Z, Sun J, et al. Advances in research on Leber's hereditary optic neuropathy[J]. Ocular Genetics and Omics, 2024, 1: 100002.