Two people with a rare inherited eye disorder have had their night vision restored by an experimental gene therapy, researchers say.
These two individuals are part of an ongoing clinical trial (opens in new tab) testing the safety and effectiveness of the new gene therapy, the research team wrote in a report published in October in the journal iScience (opens in new tab). This and additional trials will need to be completed before the therapy can be approved for widespread use, but these early data hint that the treatment can spur “remarkable gains” in patients’ night vision, the scientists wrote.
The trial participants have a genetic disorder called leber congenital amaurosis (LCA), which affects an estimated 3 in 100,000 babies, according to University of Florida Health (opens in new tab), one of the institutes involved in developing the therapy.
The disorder primarily affects the retina, the light-sensitive layers of nerve tissue at the back of the eye, and causes severe visual impairment, night or complete blindness within the first two years of life, often from the time of birth, according to the Genetic and Rare Diseases Information Center (opens in new tab). Different forms of LCA impact different genes involved in vision.
The trial participants specifically have “LCA1,” meaning they carry two defective copies of a gene called GUCY2D, which codes for a protein. Normally, light-sensitive cells in the retina shoot off an electrical signal to the brain after being exposed to light, and the GUCY2D-coded protein then helps reset the cells, preparing them to fire again. GUCY2D is especially important to rods, the light-sensitive cells that enable night vision, because it enables this cycle to unfold even in the dark.
Without a working GUCY2D gene, this cycle stalls and the cells can’t fire, according to the National Library of Medicine (opens in new tab).
Although the cells can’t fire properly, their actual structure and number remain largely unchanged; this is especially true of the rods in the retina. (There are also cones in the retina, which enable color vision, but research suggests that people with LCA1 often have marked cone loss, the researchers noted in their report.)
In theory, providing these rods with a working copy of GUCY2D could restore their ability to fire, the researchers surmised.
To deliver a working copy of GUCY2D into the retina, the researchers placed the gene inside the protective shell of a modified adeno-associated virus, a type of virus that doesn’t cause disease in humans. They then injected these DNA-carrying vessels beneath the retina; each participant received the treatment in only one eye, so their second, untreated eye could be used as a point of comparison.
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Two participants, a 19-year-old man and a 32-year-old woman, received high doses of the treatment and are the subjects of the iScience report. Prior to therapy, both had limited daylight vision but practically no night vision due to severely low light sensitivity, some 10,000 to 100,000 times below normal levels, according to Penn Medicine (opens in new tab), another institution involved in the trial.
Within eight days of treatment, both participants’ eyes became thousands of times more light-sensitive in low-light conditions, and they showed improved involuntary pupil responses to light and improvements in their ability to navigate dark rooms. Three months post-treatment, both patients’ rod sensitivity had continued to increase and the woman’s had actually neared normal levels.
These promising results add to additional data hinting at the treatment’s effectiveness, which were presented at the American Academy of Ophthalmology (opens in new tab) annual meeting in October. These earlier results showed that, in 15 total patients, the therapy caused minimal side effects, including transient inflammation, and nine patients given a high dose showed the most improvements in retinal sensitivity and vision.
But again, more research is needed before the Food and Drug Administration can assess the therapy for approval.