A gene therapy designed to treat Bothnia dystrophy, a rare form of inherited retinal disease, has shown promising results in a Phase I/II clinical trial. Led by researchers at the Karolinska Institute in Sweden, the study demonstrated that the therapy was well-tolerated and improved vision in the majority of participants.
Bothnia dystrophy is an autosomal recessive condition caused by mutations in the RLBP1 gene. It is characterized by night blindness that typically begins in early childhood and can progress to complete blindness by middle age. The condition is most prevalent in the Västernbotten region of Sweden, where it affects approximately 1 in 4,500 people. Currently, there is no effective treatment available.
The gene therapy involves an adeno-associated viral (AAV8) vector expressing a corrected RLBP1 gene. This vector is injected into the eye to deliver the functional gene to retinal cells. Preclinical studies in mice and non-human primates had previously demonstrated the safety and efficacy of this approach, showing improved dark adaptation.
The Phase I/II trial included 12 individuals with Bothnia dystrophy. The results, published in Nature Communications, indicated significant improvements in dark adaptation vision in 11 of the 12 patients. While some adverse events, such as inflammation around the injection site, were observed, they were generally mild to moderate and treatable.
"The results are important because hereditary blindness is the most common cause of blindness in younger and able-bodied people, and there is no treatment for the vast majority of those affected," said co-author Helder André, a researcher at the Karolinska Institute.
Lead author Anders Kvanta, a professor at Karolinska, added, "Our study gives hope that this large group of patients can have their vision restored in the future. The results also support the idea that gene therapy can work for hereditary diseases in general."
Building on these encouraging findings, the researchers are planning a larger study with a placebo-treated control group to further assess the therapy's efficacy and safety and to advance it toward potential market approval.
