Why the RPE65 trial? In the video below, Sander Smith (Senior Research Fellow, UCL Institute of Ophthalmology) provides an update into gene therapy research into interventions for inherited retinal diseases including an update on the results of UCL's clinical trial into RPE65 gene therapy for the treatment of Leber Congenital Amaurosis Type 2 (LCA2). Thank you to the Gene and Cell Therapy Group at UCL Institute of Ophthalmology for permission to use this video. VIDEO Why the RPE65 Trial?
Results from the world’s first gene therapy trial for inherited blindness reveal that the eyesight of people with Leber Congenital Amaurosis (LCA) can be improved at least in the short term.
Researchers at Moorfields and the UCL Institute of Ophthalmology conducted a trial that involved injecting healthy genes directly into the retinas of young patients with this progressive eye disease.
LCA is a genetic, early-onset eye condition that causes substantial sight impairment from childhood, leading to loss of night vision and progressive loss of day vision. LCA affects approximately one in 80,000 people worldwide, and it is one of the most common causes of blindness in children. There is currently no treatment for the condition.
There are numerous types of LCA, each caused by defective genes needed for normal sight. LCA Type 2, one of the more common types, is caused by a defect in the RPE65 gene (Retinal Pigment Epithelium-specific Protein 65 kDa).
This clinical trial, which involved 12 patients (6 to 23 years of age), evaluated the safety and efficacy of delivering a healthy copy of the RPE65 gene into the eye using a viral vector which is a harmless virus designed to get the RPE65 gene into the retinal cells where it is needed (Bainbridge, 2015).
Four participants in the trial received a lower dose of the vector and the remaining eight a higher dose. In each case, the eye with the poorest vision was selected for the study, with the other eye serving as a comparison. The vision of these patients was then assessed regularly over three years. References Bainbridge JWB, Mehat MS, Sundaram V, Robbie SJ et al. Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis. N Engl J Med 2015; 372:1887-1897
Results and Next Steps Temporary Improvements in Night Vision
The results from the trial revealed that half of the study’s patients experienced an improvement in their night vision, which peaked at six to 12 months after treatment before slowly declining. The improvement shown, although modest and temporary in this first study, demonstrates the potential of gene therapy treatment and paves the way for further development of this promising area.
Scientists at UCL and Moorfields have now developed a more potent gene therapy vector to deliver RPE65 genes to target cells. Researcher’s expect that the new therapy might result in greater improvements, such as a longer lasting effect or possibly even better daytime vision or even slower progression of the condition. A second trial, funded, in part, by the Medical Research Council (MRC) will test this more powerful vector.
The video below shows a participant in our clinical trial of gene therapy for sight loss navigating a maze in dim light both before and after treatment. Thank you to the Gene and Cell Therapy Group at UCL Institute of Ophthalmology for permission to use this video. VIDEO References
Bainbridge JWB, Mehat MS, Sundaram V, Robbie SJ
et al. Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis. N Engl J Med 2015; 372:1887-1897