Eye-safe gene therapy
A group of researchers from Johns Hopkins University, USA, have developed a tactic for introducing genetically engineered viruses into the space between the sclera and the vascular membrane of the eye (suprachoroidal space) with a thin needle. From there, the virus can reach the retina unhindered to deliver therapeutic genes.
The gene therapy method currently approved for the treatment of Leber congenital amaurosis is the operative introduction of a gene-carrying virus under the retina. This procedure carries a high risk of developing cataracts in patients and a low, but alarming risk of much more serious side effects – retinal detachment and other eye-threatening complications.
The new technique of injection into the suprachoroidal space, a narrow gap between the vascular membrane of the eyeball and the sclera (the outer dense shell of the eye), tested on animals, is less invasive, therefore it does not threaten possible retinal detachment and can be carried out on an outpatient basis, making therapy safer and more accessible.
The scheme of suprachoroidal injection.
The best time to start treatment for hereditary retinal degeneration using gene therapy is when the patient still has sufficiently preserved vision. But the problem is that, having high vision and agreeing to therapy, the patient may lose it due to possible complications. Having a safer and more convenient procedure in the arsenal of doctors would be a breakthrough.
According to the National Institute of Eye Research, the approach of subretinal injection of gene therapy for age-related macular degeneration, which is one of the main causes of irreversible and disabling vision loss in people over 50, is being tested in clinical trials. Approximately 10 million people in the United States suffer from age-related macular degeneration. With a more severe wet form of the disease, abnormal blood vessels grow under the retina and leak fluid, swelling of the central area of the retina develops, impairing vision. The growth of defective abnormal vessels and the exudation of fluid from them are caused by excessive production of vascular endothelial growth factor (VEGF).
Currently, to prevent vision loss, an anti-VEGF protein is injected into the eye cavity, which blocks VEGF. But the duration of this method of treatment is limited, after a few months patients are forced to return to the clinic for repeated injections. Lack of treatment can lead to the growth of abnormal vessels and further loss of vision.
Gene therapy is able to trigger the synthesis of anti-VEGF in every retinal cell, thereby preserving vision without repeated injections.
To test whether the suprachoroidal injection technique could effectively deliver components for gene therapy to the retina, the researchers first tracked whether the virus got into the back of the eye. To do this, ten rats were suprachorioidally injected with an adenoassociated virus modified to deliver a fluorescent marker. Using powerful microscopes, they tracked the glow and noted that a week later the virus had spread throughout the retina.
The researchers then tested whether the viral vector could deliver anti-VEGF genes in an experiment on 40 rat models of human age-related macular degeneration. For control, a conventional subretinal injection of 40 other rats was used.
The researchers found that the suprachoroidal injection technique was tolerated as well as the usual subretinal injection, and the effect of treatment was high and long-lasting. By repeating these experiments on pigs and rhesus monkeys, the researchers confirmed that the suprachoroidal delivery method worked in the eyes of larger animals that are closer in size to human eyes.
If the results obtained are repeated in human studies, then suprachoroidal injections will become a worthy alternative to surgical gene injection and will enable the treatment of a large number of patients with a wet form of age-related macular degeneration and hereditary diseases caused by defective genes.
Article by K. Ding et al. AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression published in the Journal of Clinical Investigation.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Johns Hopkins Medicine: Johns Hopkins Researchers Advance Search For Safer, Easier Way to Deliver Vision-Saving Gene Therapy to The Retina.