Feb 3, 2017

Scientists Are Developing an Eye Drop to Treat Inherited Blinding Eye Diseases

START therapy is a bold plan to treat inherited blinding eye disease with an eye drop. Here at Fighting Blindness Canada (FBC), we are excited about the research that Dr. Cheryl Gregory-Evans and her team are doing to make START therapy a reality. If successful, START therapy could be used to treat a variety of different genetic eye diseases, including Leber congenital amaurosis (LCA), Usher syndrome, and retinitis pigmentosa. These different degenerative diseases all share something in common: they are caused by gene mutations.

To date, researchers have identified more than 250 different genes that are involved with blinding eye diseases. Each of these genes can by mutated in a different way; basically, this means that there are different kinds of changes that are made to the DNA sequence. These changes (or “mutations”) impact the DNA’s ability to make proteins that are important for vision.

Dr. Gregory-Evans’ FBC-funded research is focused on a specific kind of mutation called a nonsense mutation. A nonsense mutation is a genetic mutation that functions as a biological stop sign. This stop sign prevents full proteins from being built and instead leads to the production of shorter, unfinished proteins. Usually, these shorter proteins don’t work. START therapy is designed to override the stop sign that is characteristic of nonsense mutations.

Aniridia is the first blinding eye disease that Dr. Gregory-Evans is testing with START therapy. People living with aniridia have a lack of iris tissue and retinal defects. Amazingly, her early success with mouse models of aniridia paved the way for a clinical trial, where her team is currently evaluating if START therapy can work as an effective treatment for people living with aniridia.

These encouraging results led Dr. Gregory-Evans to start thinking about other genetic eye diseases that might be caused by a nonsense mutation. Would START therapy work for all nonsense mutations? LCA is the next disease on her list. LCA is particularly appealing because nonsense mutations are relatively prevalent (affecting approximately 35% of people living with LCA). Moreover, there are many different animal models of LCA that were available for Dr. Gregory-Evans to use in her pre-clinical studies.

START therapy involves the use of two different drugs: Ataluren and Amlexanox. Dr. Gregory-Evans and her team are experimenting with different doses and combinations of these drugs on different disease models (including models with nonsense mutations in the RPE65 gene and the RD3 gene) to learn what works best. The end goal is to increase the production of function proteins, thereby improving vision. Dr. Gregory-Evans and her team have learned that START therapy works best if it is delivered early.

She is still working on the details for LCA, but Dr. Gregory-Evans’ encouraging results have inspired her to test START therapy with other retinal diseases, including Usher syndrome.