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Leber hereditary optic neuropathy (LHON) usually occurs in young adults. Patients affected by this condition suddenly start to lose their vision in both eyes either simultaneously or sequentially within a span of a few months. LHON is caused by a point mutation in the mitochondrial genome which leads to death or impairment of retinal ganglion cells. Researchers have found that mutation of MT-ND4 causes LHON in about 70 percent of patients.
Treatment of eye disorders using gene therapy has become popular because genes are generally injected in one eye. Even if a malfunction occurs, the other eye would remain unaffected. A Phase III gene therapy trial that focused on the study of improving vision among LHON patients was conducted. It was noted that the vision of the patients undergoing the experimental gene therapy somewhat improved in both eyes even though only one eye received treatment. The detailed outcome of the investigation, along with possible explanations, was published in Science Translational Medicine.
The main aim of the gene therapy was to administer a harmless virus containing the gene to the eye, which is subsequently taken up by retinal cells. The synthesis of protein, encoded by the gene injected, would result in preserving the retina and, thereby, bring about an improvement in vision. During the trial, researchers obtained an unexpected result. The vision of the recipients mildly improved in both eyes. Such a result implies that the inserted gene might have traveled to the untreated eye. This discovery raises concerns about the safety and the effectiveness of the therapy. The effectiveness of this therapy was hampered because the results are evaluated in comparison to the untreated eye which, as is evident, is no longer “untreated”. Hence, the treatment did not meet the original criteria of the study.
Patrick Yu-Wai-Man and his research team at the University of Cambridge are continuing their work to understand the cause of this unexpected bilateral effect. To understand the bilateral effect, they injected the virus containing the gene into one eye of three macaque monkeys and evaluated the visual systems after three months. They observed the presence of the virus in both eyes of all three animals. It was also found in their optic nerves, implying that the virus might have traveled through the optic nerves.
Thomas Corydon, Aarhus University in Denmark, who was not involved in the work, stated that he was extremely fascinated with this study. He said that the article showed substantial clinical implications that a single injection is perhaps enough for bilateral effects. Bin Li, an ophthalmologist at Tongji Hospital in China, who was also not involved with this work stated that further investigation would be required to understand the mechanism of interocular diffusion of viral DNA vector or if there exists any other mechanism by which optic nerves communicate.
At present, Yu-Wai-Man and his research team are exploring the unanswered questions and focusing on the ongoing clinical trials of this therapy.