New Gene Therapy Lights up Vision

By Drs. David Niesel and Norbert Herzog, Medical Discovery News

We all need light to see, but now a new gene therapy is restoring sight to those with vision problems by figuratively lighting up their vision.

Your vision cannot process anything without light. When light comes in contact with the cornea, the transparent outer layer of the eye, it bends the rays that pass through the pupil, the dark circle in the center of the eye. The purpose of the iris, the colored part of the eye, is to make the pupil bigger or smaller to let in enough but not too much light, like a camera.

Behind the pupil is a lens that focuses the light on the retina in the back of the eye. The retina is composed of millions of cells, some called rods and cones for their distinctive shapes, whose purpose is to sense light. The cones provide sharp vision, fine details and clear colors. The rods provide the peripheral vision, vision in dim light and the ability to see motion.

The retina converts the light entering the eye into electrical impulses and sends those to the brain through the optic nerve. The brain then deciphers the electrical signals into an image we can process.

Many different diseases can affect sight, from concussions and other brain injuries to diabetes. Lifestyle choices, such as how much or how little your eyes are exposed to the sun, also affect eye health.

Of course, our genes can play a role in how strong or poor sight is as well. Take, for example, retinal pigmentosa (RP), a group of rare genetic disorders where certain genes that encode instructions for proteins are mutated. When these proteins malfunction, the rods and cones in the retina are slowly lost, and with them, the ability to detect light. Scientists created a gene therapy that can restore the loss of light receiving cells in those with RP by targeting a gene called RPE65.

The protein this gene encodes is involved in the visual cycle, which is triggered by light entering the eye. The cycle begins when a molecule similar to vitamin A is converted to another molecule called all-trans retinal. This conversion tells the eye to send electrical signals to the brain, but for us to continue to see, the RPE65 protein has to convert the all-trans retinal back into the vitamin-A like molecule. Then it is ready to go again.

This cycle does not happen when the protein malfunctions, so the new therapy targets the protein by using an engineered virus called AAV. It's engineered to carry the normal form of the RPE65 gene. The engineered viruses are surgically introduced into the eye where they infect cells and begin making normal RPE65 proteins to correct the defect. In a clinical trial involving 21 people, all showed improved sensitivity to light. Some nearly blind patients had restored sight even three years after the therapy.

The treatment may be approved this year, but many people won't be able to afford the $100,000 cost. Still, we're excited this gene therapy works and this approach could benefit other genetic vision disorders.

Medical Discovery News is hosted by professors Norbert Herzog at Quinnipiac University, and David Niesel of the University of Texas Medical Branch. Learn more at www.medicaldiscoverynews.com.