Gene therapy to treat night blindness in dogs may be relevant in humans

Researchers have recently announced, in Proceedings of the National Academy of Sciences, that they have identified a gene therapy that returns night vision to dogs born with congenital stationary night blindness (CSNB).     

In 2015, a research team from the University of Pennsylvania’s (UPenn; PA, USA) School of Veterinary Medicine made the discovery that dogs can develop a form of inherited night blindness, which bears a strong resemblance to the condition in humans. Then, in 2019, the team identified the gene responsible. 

The novel gene therapy utilized in the most recent study targets a group of cells deep in the retina: ON bipolar cells. The researchers suggested that this represents a step towards the goal of developing a treatment for humans with this condition.  

The team previously discerned that mutations in the LRIT3 gene were the cause of CSNB in canines, and the same gene has been implicated in certain cases of human CSNB. The mutation affects the ON bipolar cells’ function, but the general structure of the retina remained intact.  

During the study, dogs with CSNB received a single injection of the gene therapy, which resulted in them beginning to express the healthy LRIT3 protein in their retinas. The therapeutic effect seems to last a year or longer.  

Researchers identified a vector for the healthy LRIT3 gene that would enable the gene therapy to enter the intended cells. In addition, the team paired the healthy gene with a promoter that would behave in a cell-specific manner.   

Keiko Miyadera, lead author of the study and assistant professor at UPenn’s School of Veterinary Medicine, stated: “we were able to treat these dogs as adults, between 1 and 3 years of age. That makes these findings promising and relevant to the human patient population, as we could theoretically intervene even in adulthood and see an improvement in night vision.” 

The researchers suggested that this is the first gene therapy that reaches the ON bipolar cells, which are located deep in the retina. William Beltran, co-author of the study and professor at UPenn’s School of Veterinary Medicine, explained: “we’ve stepped into the no-man’s land of the retina with this gene therapy, this opens the door to treating other diseases that impact the ON bipolar cells.” 

Miyadera concluded: “we had great success in this study, but we saw some dogs get better recovery than others, we’d like to continue working to maximize the therapeutic benefit while still ensuring safety. And we’ve seen that this treatment is durable, but is it lifelong after one injection? That’s something we’d like to find out.” 

In treated dogs, a healthy copy of the LRIT3 gene was only expressed as much as 30% of ON bipolar cells. Research will continue, with the aim of augmenting this uptake and amending the gene therapy to be utilized in the human version of the LRIT3 gene. In the future, this may prove a useful treatment for humans living with CSNB. 

Source: Miyadera K, Santana E, Roszak K et al. Targeting ON-bipolar cells by AAV gene therapy stably reverses LRIT3-congenital stationary night blindness. PNAS. 13 (119) (2022).