Science Sub-Journal: Shock! Clinical trials have shown that injection of gene therapy vectors into one eye can improve vision in both eyes

December 14, 2020 // --- Leber hereditary optic neuropathy, LHON, also known as Leber optic nerve atrophy, is the most common cause of mitochondrial blindness.
In a new clinical study, an international team led by Dr. Patrick Yu-Wai-Man of the University of Cambridge and Dr. Jose-Alain Sahel of the Paris Institute of Vision in France injected a gene therapy vector into one eye in patients with LHON, significantly improving vision in both eyes.
study was published in the December 9, 2020 issue of the journal Science Translational Medicine under the title "Bilateral visual improvement with gene unilateral therapy injection for Leber hereditary optic neuropathy".
images from CC0 Public Domain.
in this landmark Phase 3 clinical trial, the researchers successfully treated 37 LHON patients.
further clinical trials, the treatment could help thousands of people around the world regain and retain part of their vision.
results showed that 78 percent of PATIENT patients treated had significantly improved vision in both eyes.
suggests that the improvement in vision in an untreated eye may be due to a metastasis of viral vector DNA in the eye receiving the injection.
LHON affects a particular type of retinal cell, the retinal nerve cells, leading to rapid deterioration of optic neurodegeneration and vision in both eyes.
in the weeks following the onset of the disease, most of the affected people's vision deteriorates to the level of legal blindness.
less than 20% of cases can restore vision, and only a few have vision above 20/200 (the largest letter on the standard vision table).
incidence of LHON is about one in 30,000, mostly male, and symptoms usually occur in their twenties and 30s.
MT-ND4 gene in most patients with m.11778G-A mutations.
existing methods for treating this blinding optic neuropathy are still limited.
Sahel said, "As someone who treats these young patients, I'm very frustrated by the lack of effective treatments.
these patients quickly lose their vision over a period of weeks to months.
our research offers great hope for the treatment of this blinding disease among young people.
" the researchers injected rAAV2/2-ND4, a viral vector containing modified cDNA--- into the glass cavity at the back of one eye in 37 patients with vision loss between 6 and 12 months, and their other eye received a false injection (sham injection).
technique, known as mitochondrial targeting, was developed by the Paris Institute of Vision and licensed to GenSight Biologics.
Yu-Wai-Man, said, "We expect only the vision of one eye that receives a gene therapy vector to improve."
, 78 percent of patients in the clinical trial had their eyes improved along the same trajectory during a two-year follow-up.
"s one eye (the treatment eye) showed an average of 15 letters better corrective vision (best-corrected visualization, BCVA) on the ETDRS vision table with three lines of vision, while the eye receiving the fake injection (the false therapeutic eye) improved by an average of 13 letters.
Because some patients are still in the dynamic stage of the disease process at the time of registration, the improvement in vision from the lowest point (the worst BCVA per eye) is even greater: the therapeutic eye reaches 28.5 letters and the false therapeutic eye reaches 24.5 letters.
Yu-Wai-Ma said, "By replacing the defective MT-ND4 gene, this treatment can save retinal nerve cells from the devastating effects of the m.11778G-A mutation, preserve function and improve the patient's visual prognosis."
result is that it can change the lives of patients.
researchers found that the chances of treating the eye to 20/200 with better or equal vision increased about threefold.
the results of the patient's report were evaluated using the National Eye Institute Visual Function Questionnaire-25,NEI VFQ-25, which also confirmed that the treatment had a positive impact on the quality of life and socio-mental health of the patient.
, the researchers conducted a study in crab-eating monkeys to see how treatment of one eye could lead to improvements in the other.
system of crab-eating monkeys is similar to that of humans, which allows for more detailed studies of the distribution and effects of gene therapy vectors.
one-eye injection rAAV2/2-ND4, after 3 months, tissues from various parts of the eye and brain were analyzed and the presence of viral vector DNA quantitatively detected using genetically modified specific quantitative PCR testing methods.
virus vector DNA was detected in the front, retina and optic nerve of an untreated eye of a crab monkey.
, unexpected visual improvements observed in an untreated eye may reflect inter-eye diffusion of rAAV2/2-ND4.
further investigation is needed to confirm these findings and whether there are other mechanisms that lead to this improvement in the eyes.
Yu-Wai-Man said, "It has become a reality to save vision with gene therapy.
the treatment has been shown to be safe and we are currently exploring the best treatment window.
," Dr. Sahel added, "our approach is not limited to restoring vision."
other mitochondrial diseases may also be treated with the same techniques.
(Bioon.com) : 1. Patrick Yu-Wai-Man et al. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Science Translational Medicine, 2020, doi:10.1126/scitranslmed.aaz7423.2.Gene therapy injection in one eye surprises scientists by improving vision in both。