The patients had Leber Congenital Amaurosis (LCA), a genetic blindness triggered by GUCY2D gene mutations. The researchers administered AAV gene therapy, which includes the DNA of the healthy kind of the gene, into the retina of one eye for each of the patients in line with the clinical trial procedure. While the extent of vision loss may vary from patient to patient with LCA, all such individuals experience significant visual impairment starting in the very first few months of life. The scientists administered the therapy to just one eye in each patient, so the treated eye could be compared to the neglected eye to gauge treatment results. To the researchers, the outcomes validate that GUCY2D gene therapy restores rod-based photoreceptor functions– and recommend that GUCY2D– LCA clients with more serious rod-based dysfunction are most likely to benefit most dramatically from the therapy.
. While the level of vision loss may differ from client to client with LCA, all such individuals experience substantial visual disability beginning in the very first few months of life.
As much as 20 percent of LCA cases are caused by mutations in GUCY2D, a gene that encodes a crucial protein needed in retinal photoreceptor cells for the “phototransduction waterfall”– the process that converts light to neuronal signals. Prior imaging studies have revealed that patients with this kind of LCA tend to have relatively preserved photoreceptor cells, specifically in rod-rich areas, hinting that rod-based phototransduction could work again if functional GUCY2D existed. Early outcomes with low dosages of the gene treatment, reported last year, followed this idea.
The researchers utilized greater dosages of the gene therapy in 2 clients, a 19- year-old male and a 32-year-old woman, who had especially extreme rod-based visual deficits. In daytime, the patients had some, albeit significantly impaired, visual function, but in the evening they were effectively blind, with light sensitivity on the order of 10,000 to 100,000 times less than regular.
The researchers administered the therapy to simply one eye in each patient, so the treated eye could be compared to the neglected eye to determine treatment results. Tests revealed that, in both patients, the treated eyes ended up being thousands of times more light-sensitive in low-light conditions, substantially fixing the initial visual deficits. The scientists used, in all, nine complementary approaches to determine the clients light sensitivity and practical vision.
” Just as striking was the rapidity of the improvement following therapy. Within 8 days, both patients were currently revealing quantifiable effectiveness,” stated research study co-author Artur V. Cideciyan, Ph.D., a research professor of Ophthalmology at Penn
. To the scientists, the results confirm that GUCY2D gene treatment brings back rod-based photoreceptor functions– and suggest that GUCY2D– LCA patients with more extreme rod-based dysfunction are likely to benefit most dramatically from the treatment. The useful message is that there should be an emphasis on rod vision measurements at the screening of LCA prospects and in monitoring them throughout a treatment trial.
The findings, the researchers stated, likewise underscore the remarkable reality that in some patients with severe genetic vision loss, the retinal cell networks that moderate vision remain mainly alive and undamaged, and need only the resupply of a missing protein to start working once again, more or less right away.
Referral: “Night vision restored in days after decades of congenital blindness” by Samuel G. Jacobson, Artur V. Cideciyan, Allen C. Ho, Alejandro J. Roman, Vivian Wu, Alexandra V. Garafalo, Alexander Sumaroka, Arun K. Krishnan, Malgorzata Swider, Abraham A. Mascio, Christine N. Kay, Dan Yoon, Kenji P. Fujita, Sanford L. Boye, Igor V. Peshenko, Alexander M. Dizhoor and Shannon E. Boye, 3 October 2022, iScience.DOI: 10.1016/ j.isci.2022.105274.
The continuous medical trial is registered at clinicaltrials.gov as trial NCT03920007.
The study was moneyed by Atsena Therapeutics, Inc., the designer of the GUCY2D gene therapy; the National Institutes of Health; and by the Pennsylvania Department of Health.
The clients had some, although badly reduced, visual function during the day, nevertheless, at night they were basically blind, with light sensitivity 10,000– 100,000 times less than regular.
The patients had Leber Congenital Amaurosis, a type of genetic congenital blindness.
According to researchers at the Scheie Eye Institute at the Perelman School of Medicine at the University of Pennsylvania, adults with a genetic type of childhood-onset loss of sight experienced impressive recoveries of night vision within days of getting a speculative gene therapy.
The patients had Leber Congenital Amaurosis (LCA), a congenital blindness triggered by GUCY2D gene anomalies. The researchers administered AAV gene treatment, which contains the DNA of the healthy form of the gene, into the retina of one eye for each of the clients in line with the clinical trial protocol.
” These amazing outcomes show that the standard molecular equipment of phototransduction remains largely intact in some cases of LCA, and hence can be amenable to gene therapy even after years of loss of sight,” said study lead author Samuel G. Jacobson, MD, Ph.D., a professor of Ophthalmology at Penn
