A gene therapy for an inherited eye disorder can ameliorate vision loss in both eyes despite only being injected into one, according to a phase 3 clinical trial involving 37 patients. The treated patients showed sustainable improvements in vision after 96 weeks, providing evidence the gene therapy could offer a safe and effective therapy for Leber hereditary optic neuropathy (LHON), an inherited blinding disease with few treatments. The study also yields clues about why the treatment unexpectedly seemed to work in both eyes, a finding that could guide future research into similar treatments. Gene therapies with viral vectors have been tested as interventions for an array of genetic disorders, including LHON. Although scientists are still refining gene therapy approaches, there has been substantial progress over the past decade, and some treatments have begun to enter the final phases of clinical testing. Patrick Yu-Wai-Man and colleagues treated 37 patients with vision loss due to LHON with a viral vector that corrects genetic defects in mitochondria, the energy producers of cells. Surprisingly, 78% of the patients showed improvements in vision in both eyes after 96 weeks with only mild side effects, even though the therapy was only injected into the right eye of each subject. The scientists explored this finding more in nonhuman primates and reported that DNA from the vectors could be found in both treated and untreated eyes. At the end of the study, the patients also reported improvements in independence, mental health, general vision, and other quality-of-life metrics. Yu-Wai-Man et al. caution their study lacked a true prospective control group, and recommend conducting further trials to pin down the mechanisms that enabled both eyes to improve.
Science Translational Medicine