Developments in the Treatment of Leber Hereditary Optic Neuropathy

Purposeof Review To outline the current landscape of treatments for Leber hereditary optic neuropathy (LHON) along the therapeutic delivery pipeline, exploring the mechanisms of action and evidence for these therapeutic approaches. Recent Findings Treatments for LHON can be broadly classified as either mutation-specific or mutation-independent. Mutation-specific therapies aim to correct the underlying mutation through the use of a gene-editing platform or replace the faulty mitochondrial DNA-encoded protein by delivering the wild-type gene using a suitable vector. Recent gene therapy clinical trials assessing the efficacy of allotopically expressed MT-ND4 for the treatment of LHON due to the m.11778G > A mutation in MT-ND4 have shown positive results when treated within 12 months of symptom onset. Mutation-independent therapies can have various downstream targets that aim to improve mitochondrial respiration, reduce mitochondrial stress, inhibit or delay retinal ganglion cell apoptosis, and/or promote retinal ganglion cell survival. Idebenone, a synthetic hydrosoluble analogue of co-enzyme Q(10) (ubiquinone), is the only approved treatment for LHON. Mutation-independent approaches to gene therapy under pre-clinical investigation for other neurodegenerative disorders may have the potential to benefit patients with LHON. Although approved treatments are presently limited, innovations in gene therapy and editing are driving the expansion of the therapeutic delivery pipeline for LHON.

Automated summary

This review outlines the current landscape of treatments for Leber hereditary optic neuropathy (LHON). The treatments can be classified as either mutation-specific or mutation-independent. Mutation-specific therapies aim to correct the underlying mutation, while mutation-independent therapies aim to improve mitochondrial function. Currently, only one drug is approved for LHON treatment. However, innovations in gene therapy and editing are driving the expansion of therapeutic options.