In a small and preliminary clinical trial, Johns Hopkins researchers and their collaborators have shown that an experimental gene therapy that uses viruses to introduce a therapeutic gene into the eye is safe and that it may be effective in preserving the vision of people with wet age-related macular degeneration (AMD).
The disease is marked by growth of abnormal blood vessels that leak fluid into the central portion of the retina called the macula, which we use for reading, driving and recognizing faces.
The study, published in The Lancet, reports an exciting new approach in which a virus, similar to the common cold, but altered in the lab so that it is unable to cause disease, is used as a carrier for a gene and is injected into the eye. The virus penetrates retinal cells and deposits a gene, which turns the cells into factories for productions of a therapeutic protein, called sFLT01.
The abnormal blood vessels that cause wet AMD grow because patients have increased production of vascular endothelial growth factor (VEGF) in their retinas.
Current treatments require injections of proteins directly into the eye that bind and inactivate VEGF, reducing fluid in the macula and improving vision. However, the therapeutic proteins exit the eye over the course of a month, so patients with wet AMD usually need to return to the clinic for more injections every six to eight weeks in order to stave off vision loss.
Eye specialists say the burden and discomfort of the regimen is responsible for many patients not getting injections as frequently as they need, causing vision loss.
Because viruses naturally penetrate cells and leave behind genetic material, the investigators designed their virus to target retinal cells and provide them with a gene that produces sFLT01. Thus, retinal cells become factories that produce the therapeutic protein — potentially eliminating the need to repeatedly inject it.
‘This preliminary study is a small but promising step towards a new approach that will not only reduce doctor visits and the anxiety and discomfort associated with repeated injections in the eye, but may improve long-term outcomes because prolonged suppression of VEGF is needed to preserve vision, and that is difficult to achieve with repeated injections because life often gets in the way,’ explained Peter Campochiaro, MD, the George S and Dolores D Eccles Professor of Ophthalmology at the Johns Hopkins University School of Medicine.