Gene therapy shows promise in initial trial for patients with childhood blindness – sciencedaily

According to initial data from a clinical trial conducted by researchers at the Scheie Eye Institute at the Perelman School of Medicine at the University of Pennsylvania, a new gene therapy for one of the most common forms of congenital blindness was safe and improving the vision of patients.

The therapy delivers working copies of GUCY2D to the eyes of patients with severe visual disturbances caused by mutations in the gene. Each of the first three patients treated experienced improvement in some aspect of vision, without serious side effects, according to the new study published in the journal iScience.

“We have seen lasting improvements in day and night vision, even with a relatively low dose of gene therapy,” said study lead author Samuel G. Jacobson, MD, PhD, professor of ophthalmology at the Perelman School of Medicine.

The GUCY2D gene is one of about 25 different human genes whose mutations cause problems in the retina, leading to severe visual impairment from birth or infancy. This family of inherited retinal disorders, collectively known as Leber’s congenital amaurosis (CVA), accounts for a significant portion of blindness in children worldwide.

Normal copies of GUCY2D encode an enzyme in the key pathway that light-sensitive rod and cone cells in the retina use to convert light into electrochemical signals. A lack of this enzyme blocks the recovery of this pathway, preventing the reset needed for further signaling. As a result, the signal from rod and cone cells becomes very weak – equivalent to severe vision loss.

Even in adults who have lived for decades with this disease, it is often the case that many light-sensitive retinal cells remain alive and intact despite their dysfunction. Thus, adding functional copies of GUCY2D via gene therapy could allow these cells to function again and restore some vision.

In 2019, Jacobson and co-investigator Artur V. Cideciyan, PhD, research professor of ophthalmology at the Perelman School of Medicine, began the first clinical trial of GUCY2D gene therapy, a solution of a harmless virus that carries gene and is injected under the retina – initially in one eye per patient. They follow each patient for two years after treatment. In the new report, they described their results after nine months in the first three patients treated.

The first patient experienced a substantial increase in light sensitivity in rod cells, which are more sensitive to light than cone cells and are primarily responsible for low light or “night vision”. This patient also showed improvement in pupil responses to light.

The second patient showed a smaller but sustained increase in light sensitivity in rod cells, starting about two months after gene therapy.

The third patient showed no improvement in rod cell sensitivity, but showed significantly improved visual acuity over the nine-month follow-up period, an improvement the researchers linked to better cone cell function. of the patient, the predominant cells for daylight and color. vision.

“These early results from the very first trial of a GUCY2D gene therapy are very encouraging and will inform our ongoing and future trials of this therapy,” said Cideciyan. There were no serious unwanted side effects and the side effects that occurred in the retina of the patients disappeared.

The dose of gene therapy used in these first three patients was the lowest of the doses the researchers plan to use in the study, so they hope to see continued safety and greater efficacy in patients recruited later who will receive drugs. higher doses.

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