Two people with a rare heredity eye disorder have recovered their night vision through an experimental gene therapy, researchers say.
These two people 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). These and additional studies will need to be completed before the therapy can be approved for widespread use, but these early data indicate that the treatment could produce “remarkable gains” in patients’ night vision, the scientists wrote.
The trial participants have a genetic condition called leber congenital amaurosis (LCA), which is estimated to affect 3 in 100,000 babies, according to University of Florida Health (opens in new tab)one of the institutes involved in the development of the therapy.
The condition primarily affects the retina, the light-sensitive layers of nerve tissue at the back of the eye, causing severe visual impairment, night blindness or complete blindness within the first two years of life, often from the time of birth, according to the Information Center for Genetic and Rare Diseases (opens in new tab). Different forms of LCA affect different genes involved in vision.
The test 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 send an electrical signal to it brain after being exposed to light, and the GUCY2D-encoded protein then helps reset the cells and prepare them to fire again. GUCY2D is especially important for rods, the light-sensitive cells that enable night vision, because this cycle can unfold even in the dark.
Without a working GUCY2D gene, this cycle stops and the cells cannot fire, according to the National Library of Medicine (opens in new tab).
Although the cells cannot fire properly, their actual structure and number remain largely unchanged; this is especially true for 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, supplying these rods with a working copy of GUCY2D could restore their ability to fire, the researchers suspected.
To deliver a working copy of GUCY2D into the retina, the researchers placed the gene in the protective shell of a modified adeno-associated virus, a type of virus that does not cause disease in humans. They then injected them DNA-carrying vessels under 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 subject of the iScience report. Prior to therapy, they both had limited daylight vision, but virtually no vision at night due to very 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 process.
Within eight days of treatment, both participants’ eyes became thousands of times more sensitive to light in low light, and they showed enhanced involuntary pupil responses to light and improvements in their ability to navigate dark rooms. Three months after treatment, both patients’ sensitivity to rods had continued to increase, and the woman’s was even close to normal.
These promising results add to additional data pointing to the treatment’s effectiveness, which were presented at the American Academy of Ophthalmology (opens in new tab) annual meeting in October. These previous results showed that the therapy produced minimal side effects, including transient ones, in a total of 15 patients inflammationand nine high-dose patients showed the most improvements in retinal sensitivity and vision.
But again, more research is needed before the Food and Drug Administration can review the therapy for approval.