Nov 30, 2016

Top 10 Discoveries Driving the Race to Restore Sight in 2016

At the Foundation Fighting Blindness (FFB) we are motivated by a singular goal: develop new treatments for blindness and vision loss. This goal fuels all of the research that we fund. Today, we know more about blinding eye diseases than ever before. This knowledge is power because it shows us where to direct our resources to win the fight against blindness.

There are four top contenders in the Race to Restore Sight:

• Gene therapies
• Stem cell therapies
• Drug therapies
• Artificial vision

The countdown below showcases the Top 10 FFB discoveries from 2016 that are driving the race to restore sight.

GENE THERAPIES
Although we are not quite ready to declare a clear winner in the race to restore sight, many experts believe that gene therapy is the leading the way. 2016 was a year of encouraging research and clinical developments, including the launch of the first optogenetics-based gene therapy to restore vision, and the promise of new gene editing technologies, such as CRISPR. Two FFB-funded discoveries helped to ensure the future success of gene therapy.

10. Dr. Ian MacDonald completed the first year of his two year ocular gene therapy trial for choroideremia patients. By pioneering Canada’s first ocular gene therapy trial, Dr. MacDonald and his team are paving the way for gene therapies in general. It is hard work to be first – but we are so proud to have Dr. MacDonald leading the way! Dr. MacDonald is not able to share his results until after the study is completed, but we can’t underestimate the value of his pioneering work which is discovering the path forward for gene therapies in Canada. Read more.

9. Dr. Andras Nagy is a world leader in stem cell therapeutics – but his work also combines gene therapy. Dr. Nagy and his team are working to generate a safe and “smart” stem cell therapy to treat age-related macular degeneration. To do this, they are using gene editing techniques to make stem cell therapies safer and also allow them to release sight-saving drugs – specifically to treat wet age-related macular degeneration. This year, they discovered that their genetically modified stem cells are able to release the drug and also survive for a long-term after they have been grafted. This new evidence that their approach is both safe and effective is essential in the development of a “one-shot” treatment for AMD. Read more.

STEM CELL THERAPIES
It was a whirlwind year for stem cell therapeutics. Game-changing discoveries rocked the stem cell world and also identified key challenges and opportunities for stem cell-based vision therapies. In 2016, four FFB-funded researcher projects helped to solidify Canada as an international leader on the stem cell stage.

8. Dr. Valerie Wallace’s stem cell research is focused on replacing the eye’s precious cone photoreceptors, which are essential for central, high acuity and colour vision. The loss of cones causes central vision loss in AMD and in late stage retinitis pigmentosa. By studying the function of novel cone-specific genes they are gaining critical insights into cone biology and survival. This research has the potential to identify novel approaches to promote cone survival. This year, Dr. Wallace developed a new model to study cones that will be used be researchers around the world to fine-tune stem cell transplantation methods.

7. Dr. Gilbert Bernier is also focused on cone photoreceptors. (Cones are so critically important to restoring vision, we need lots of people focused on this problem.) We are thrilled that Dr. Wallace and Dr. Bernier are collaborating to accelerate their progress. In 2015, we reported that Dr. Bernier had developed a new method to produce large numbers of cones for transplantation therapy. This year, Dr. Bernier identified the best pre-clinical animal models that will be needed before moving into a clinical trial with humans and began assembling a team of surgical experts to conduct the work.

6. Dr. Michel Cayouette is also working on stem cell transplantation, but from a slightly different approach. Because we don’t know who is going to win the race to restore sight, we know that investing in different, complementary strategies is key for long-term success. In 2016, Dr. Cayouette discovered key genes that are involved in the development of photoreceptors: specifically the genes that cause a photoreceptor to become a cone or a rod. Controlling this developmental pathway could inform the development of effective, efficient stem cell therapies. Read more.

5. Dr. Sarah McFarlane is also studying development to learn how eye cells migrate during regular development and during injury. This year, she discovered key information about the behaviour of very early cells that are destined to develop into retinal pigment epithelium (RPE cells). It’s very important to understand how RPE cells move and function because they are currently being tested as a potential stem cell-derived treatment in clinical trials for AMD and Stargardt disease. Building on her discovery, Dr. McFarlane is now engineering new tools to live-track cells. These new tools will help to uncover information to guide the development of safe and effective stem cell therapies. Read more.

DRUG THERAPIES
Scientists are working to identify and develop new drug with the capacity to preserve remaining vision and prevent further vision loss. In 2016, three FFB-funded researchers made critical steps toward making new drug therapies for blinding eye diseases a reality.

4. Dr. Cheryl Gregory-Evans is developing a drug that would address one type of disease-causing mutation, known as a “nonsense” mutation, which is responsible for approximately 35% of all cases of Leber congenital amaurosis (LCA). Nonsense mutations cause premature stop signs, which lead to non-functional proteins. The absence of these necessary proteins cause disease. Dr. Gregory-Evans is pioneering a nonsense read-through therapy, which uses drugs that allow the cellular machinery to ignore the incorrect stop sign and produce full-length, functional proteins. This year, her team made key progress with their discovery that if the drugs are given early enough then the retina can be preserved. This positive data with their work on LCA means that they can test this drug combination approach for other retinal diseases!

3. Dr. Bruno Larrivée is developing a new drug treatment for age related macular degeneration. This year his team made key progress with their discovery that BMP9 is just as efficient as current anti-VEGF agents to prevent blood vessel growth, but doesn’t have the disadvantages of these agents, such as the injection method that is used to deliver current anti-VEGFs. This research defines a new strategy to prevent the growth of pathological blood vessels in wet AMD.

2. Dr. Jean-Sébastien Joyal’s discovery in 2016 has fundamentally changed how we understand wet age-related macular degeneration (AMD). His work established several groundbreaking findings—which is why this research was featured on the cover of the prestigious journal Nature Medicine. First, it was shown that photoreceptors use an alternative pathway (lipid β-oxidation), in addition to glucose metabolism, to produce energy. Second, by genetically and pharmacologically manipulating this pathway to simulate nutrient scarcity, researchers were able to show that starving photoreceptors increases production of VEGF – the signaling molecule associated with AMD-causing blood vessel proliferation. Finally, it was shown that this increase in VEGF by energy deficient photoreceptors causes wet AMD-like retinal lesions. These findings provide strong evidence for a previously unknown mechanism underlying wet AMD that will open avenues to future sight-saving treatment strategies.

1. Stay tuned! Our biggest, most exciting discovery of the year is still TOP SECRET! We will be announcing it before the end of 2016.

ARTIFICIAL VISION
In people living with an advanced retinal disease, the light-capturing cells of the retina, called photoreceptors, have been lost, but the network of nerves that sends visual information to the brain is often intact. Artificial vision uses electronic devices that are able to bypass the photoreceptors and send visual signals directly to the brain. The success of artificial vision depends on our in-depth understanding of how vision works. In 2016, FFB-funded researchers made 42 new discoveries that are helping us to understand vision. If you don’t know what’s broken – you can’t fix it. All of these discoveries are increasing the success of future treatments.

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