A phase I clinical trial in the US has successfully used gene therapy to improve vision in individuals suffering from a rare form of hereditary blindness. The promising results of this trial pave the way for future trials and may eventually lead to a cure for several forms of congenital blindness.
The study, supported by the US National Eye Institute (NEI), was conducted at the University of Pennsylvania and the University of Florida. Three individuals aged 22, 24 and 25, who were registered as legally blind since birth due to a condition called Leber's congenital amaurosis (LCA), were treated with gene therapy to correct the genetic defect that caused their loss of vision. One year after treatment there was no indication of negative side effects caused by an immune response to the corrective DNA in any of the patients and, although the patients' ability to read an eye chart was unchanged, they were all able to detect dim lights that they could not see before the therapy. One patient was reportedly able to read an illuminated digital clock on the dashboard of a car for the first time.
Professor Artur Cideciyan, a leading member of the research team, said: 'At one year... [this] gene therapy appears to be safe and leads to a stable visual improvement in the patients studied. We are cautiously optimistic about these results and look forward to additional reports that address the key issues of safety and effectiveness'.
The three patients all suffered from LCA due to defects in a gene called RPE65, which is makes a form of vitamin A that is essential for the functioning of light-detecting cells in the eye. The researchers used a genetically engineered virus as a vehicle to deliver corrected versions of RPE65 to certain areas of the eye where these cells were still intact enough to be good candidates for repair. They found that the woman who gained the ability to read the car clock showed signs that her brain was re-training itself to use only the corrected areas of her eye. Professor Samuel Jacobson, who led the trial, commented that 'this... finding shows that over time, a person visually adapted to gene therapy in a meaningful way. As we continue our studies, we will look more closely at whether these slow visual gains could be accelerated with visual training'.
The three patients will continue to be monitored for several years to ensure the therapy's safety and to determine how long-lasting the improvements in their vision are. Further trials of this therapy are also underway. Dr Paul Sieving, director of the NEI, said: 'These results are very significant because they represent one of the first steps toward the clinical use of gene therapy for an inherited form of blindness. I anticipate that it is only a matter of time before similar techniques will be applied to other genetic diseases affecting vision.'