The vision of three adults who underwent gene therapy for Leber congenital amaurosis type 2 (LCA2) in their worse eyes have progressed further after receiving gene therapy in their second eyes, according to a report published on February 8 online in Science Translational Medicine.
LCA2 is one of at least 15 types of the genetic disorder, which disrupts transmission of light to the retina, impairing vision in childhood and leading to total blindness.
The new study, by Jean Bennett, MD, PhD, at the University of Pennsylvania, Philadelphia, and the Children’s Hospital of Philadelphia, Pennsylvania, and colleagues, continues a phase 1/2 clinical trial that treated the worse eyes in 12 individuals, all of whom improved shortly after receiving 1.5 × 1010 to1.5 × 1011 adeno-associated virus (AAV) vectors via subretinal injection.
The researchers performed gene therapy on the contralateral eyes of three of the initial 12 patients to assess immune response to the vector 1.7 to 3.3 years after initial treatment.
Vision includes many parameters, including depth perception and identification of edges and movement. These circuits may develop the best if both eyes are functioning at a certain level
In all three patients, vision improved, particularly for light sensitivity, with no adverse effects or migration of virus beyond the eye. Lead investigator Manzar Ashtari, PhD, from the Department of Radiology at the Children’s Hospital of Philadelphia, told Medscape Medical News, “It was exciting to see how the brain responds. The eye is an extension of the brain, so if there’s manipulation in the eye, the brain knows. The before-and-after fMRIs are like day and night. This is how these patients are.”
The patient who received the highest initial AAV dose improved to the greatest extent. Moreover, in all three patients, the first-treated eyes improved further after treatment of the second eyes; for example, decreasing the amplitude of nystagmus. Dr. Bennett speculated that this finding may reflect plasticity in the nervous system. “Vision includes many parameters, including depth perception and identification of edges and movement. These circuits may develop the best if both eyes are functioning at a certain level,” she said.
One patient improved in sensitivity to red, indicating involvement of cones. “Perhaps red sensitivity picked up because there are twice as many red cones as other colors in the human eye,” said Dr. Ashtari. He said that in addition to being safe and effective, the gene therapy appears to be long-lasting.
Although the US Food and Drug Administration has yet to approve any gene therapy, the researchers are already developing a training program.
