French researchers at the Institut de la Vision have pioneered an innovative gene therapy that restores vision for patients with Leber's hereditary optic neuropathy (LHON), a rare genetic condition. Promising clinical trials pave the way for potential commercialization.
LHON is a rare hereditary disorder that strikes in adolescence, causing sudden bilateral vision loss that can lead to blindness. Triggered by mutations in mitochondrial DNA, it disrupts ND4 protein production and primarily affects young men—first one eye, then the other weeks or months later. It occurs in roughly 1 in 30,000 to 50,000 people. As noted by Handicap.fr on December 12, 2020, Paris-based Institut de la Vision, partnering with startup GenSight Biologics, has developed a novel treatment targeting the mitochondrial ND4 gene defect for the first time.
Gene therapy introduces therapeutic genetic material into cells using viral vectors to deliver DNA to the nucleus. The challenge: directing it specifically to mitochondria. Researchers overcame this with an ingenious solution.
The key innovation? Adding specialized DNA "address sequences" to the gene, enabling genetic material to transform into functional proteins directly in mitochondria. An international phase III clinical trial, led by the UCL Institute of Ophthalmology and involving 37 patients (named RESCUE), confirmed its efficacy. Remarkably, injecting the therapy into one eye improved vision in both eyes for over 75% of participants.
This unexpected bilateral effect prompted further animal studies by GenSight Biologics, revealing transfer of the healthy gene between eyes. These findings offer hope for LHON patients, who previously had no effective treatments. Ongoing research may extend this approach to other mitochondrial diseases affecting various tissues.
