Gene therapy for Leber’s hereditary optic neuropathy cannot be stopped… » Medvestnik


Gene therapy for Leber’s hereditary optic neuropathy was found to be safe but did not prevent or slow loss of visual acuity. Scientists plan to test other treatment approaches, including editing the mitochondrial genome.

Gene therapy for Leber hereditary optic atrophy appeared safe but did not show significant efficacy, said researchers from the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine. The study results were published on the National Institutes of Health website with reference to the American Journal of Ophthalmology.

Although some participants reported improvement in vision with therapy, patients with minimal impairment (Snellen score of 20/40 or better) at study entry were unable to maintain or slow their decline in visual acuity. The loss was approximately 3 rows on the table within 12 months after the start of therapy.

Adverse events during treatment were limited to uveitis, which occurred in 71% of participants receiving high doses of the gene vector and in 15% of other patients.




Leber’s hereditary optic neuropathy is a rare disease caused by mutations in mitochondrial DNA. In order to restore the function of the ND4 gene, patients were injected with a viral vector (AAV2) carrying the normal gene into the left or right eye. After injection, the vector delivered the gene to the retinal ganglion cells, where it was integrated into the DNA of the cell nucleus.

The phase 1 gene therapy study included 28 patients with Leber hereditary optic atrophy. Chronic bilateral vision loss was detected in 11 cases, acute bilateral vision loss in 9 people, and unilateral vision loss in 8 patients. Participants received 4 therapeutic doses of the drug with different concentrations of the gene vector. The observation continued for three years. The researchers tracked adverse events, changes in vision, including visual acuity, and immune response to treatment.

According to Byron Lamb (Byron Lam) from the University of Miami, gene therapy turned out to be safe, but its effect can be called, at best, modest – regardless of the dose. Scientists are considering alternative approaches to therapy, including mitochondrial genome editing.



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