Two young sisters with a blinding eye condition will now have access to ocular gene therapy after a new pathway to the treatment was discovered.

The girls, who were diagnosed with early-onset severe retinal dystrophy (EOSRD), an inherited degenerative disease of the retina, began having trouble with their night vision at four and two years of age.

With few effective treatments available for retinal dystrophies, their vision was expected to continue to deteriorate over time. However, the discovery of two potential variants in the RPE65 gene has changed everything.

While initial genetic testing was unable to identify a clear-cut genetic cause for their disorder, the potential variants opened the possibility for treatment using radical ocular gene therapy, LUXTURNA.

LUXTURNA is a world-first gene replacement therapy for an RPE65-related retinal vision loss. It works by injecting LUXTURNA under the retina and carrying a functioning RPE65 gene to replace the faulty one, preventing severe vision loss and eventual blindness.

This life-changing breakthrough was made as part of a study led by a team of researchers across Kids Research at Sydney Children’s Hospitals Network (SCHN), the Children’s Medical Research Institute (CMRI) and the University of Sydney (USyd). This included Professor Robyn Jamieson (SCHN, CMRI and USyd), PhD student Benjamin Nash (USyd, CMRI), Dr Anai Gonzalez Cordero (CMRI) and Associate Professor Seo-Kyung Chun (KR, SCHN).

Prof Robyn Jamieson, who is also the lead of Ocular Gene and Cell Therapies Australia (OGCTA) and Eye Genetics Research Unit, said the findings of the study were incredibly promising and would help pave the way for treating patients with all kinds of retinal dystrophies moving forward.

“To have an approach and a strategy is really useful and it will create a pipeline for more patients with these types of conditions and in cases where we need to find the genetic answer, because there are clinical therapies available,” Prof Jamieson said.

The study was able to determine both variants were pathogenic, or disease-causing. Previously only one had been connected to the disease.

Researchers did this by taking blood cells from one of the parents, who is a carrier of the disease, and transformed them into stem cells, which could then be differentiated into the eye tissue where the RPE65 gene is found.

Using techniques on the RNA, which is described as the voice of the DNA, the team were then able to identify the unknown variant and link it to the mutation.

“By determining that both variants were in fact pathogenic, we could open up the possibility of therapy for the sisters,” Prof Jamieson said.

Now eligible for LUXTURNA, the sisters will begin to prepare to receive the gene therapy, a procedure that will happen at The Children’s Hospital at Westmead as part of OGCTA.

OGCTA is a collaboration involving the Genetic Eye Clinic at SCHN, the Eye Genetics Research Unit and Stem Cell Medicine Group at CMRI, and the Save Sight Institute at Sydney Eye Hospital and University of Sydney. It has already successfully delivered LUXTURNA to two teen siblings earlier this year, with the therapy helping to stop their progressive vision loss and even leading to improvements in their sight.

This study has been published in Hindawi, Stem Cells International and was partly funded by Luminesce Alliance.