Developments in the Treatment of Leber Hereditary Optic Neuropathy

AbstractPurposeof ReviewTo 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 FindingsTreatments 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 expressedMT-ND4 for the treatment of LHON due to the m.11778G  >  A mutation inMT-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 hydrosolub le analogue of co-enzyme Q10 (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.SummaryAlthough approved treatments are presently limited, innovations in gene therapy and editing are driving the expansion of the therapeutic del...
Source: Current Neurology and Neuroscience Reports - Category: Neuroscience Source Type: research