Dr. José Sahel

If you or someone you’re close to has a retinal degenerative disease, you should know about the vision-saving promise of a protein called Rod-derived Cone Viability Factor (RdCVF). It was discovered by Foundation-funded clinician-researchers Drs. José Sahel and Thierry Léveillard, of Institut de la Vision in Paris. In fact, they won the Foundation’s Board of Director’s Award in 2005 for the finding. It was a monumental effort, namely because they screened thousands of proteins to come up with the gem.

In a poster at ARVO, researchers show how they’ve provided sustained delivery of RdCVF through gene therapy, which has performed well in preserving and restoring cones, the retinal cells that give us central and color vision and the ability to see details. Most excitingly, this therapy is poised to move into a clinical trial.

RdCVF works independently of the genetic defect causing the retinal disease, meaning that it has great potential to help people with a wide variety of retinal conditions. While this study was performed in an animal model for retinitis pigmentosa, it is the kind of study that helps lay the scientific foundation needed for using the treatment in humans.

The ARVO poster highlights a collaborative effort that includes Drs. Sahel and Léveillard, and Dr. John Flannery of the University of California, Berkeley.

Dr. Robert MacLaren

I was very excited to learn here at ARVO that two early-stage gene therapy clinical trials – one for choroideremia taking place in the U.K., the other for autosomal recessive retinitis pigmentosa (arRP) caused by MERTK mutations underway in Saudi Arabia – are proceeding well thus far. It is important to keep in mind that safety is the primary focus in these Phase I studies.

Dr. Emad Abboud, from the King Khaled Eye Specialist Hospital in Riyadh, reported that three patients, all in their thirties, have been treated with the MERTK gene therapy. The treatment uses an adeno-associated virus 2 (AAV2) – similar to the AAV2 used in landmark vision-restoring gene therapy clinical trials for Leber congenital amaurosis – to deliver copies of the therapeutic gene to retinal pigment epithelial cells in the retina.

Thus far, the MERTK treatment has been safe in all three patients. The two patients who received the treatment in 2011 have reported that they are seeing better with their treated eye and can read more lines on an eye chart than they could before the treatment. One woman said, “I see with the operated eye many things in the kitchen that I couldn’t see before.” The third patient, treated in April 2012, has not had his vision tested since receiving the therapy.

This study is being performed in collaboration with Dr. Kang Zhang at the University of California, San Diego.

Dr. Robert MacLaren, who is conducting the choroideremia gene therapy clinical trial at Moorfields Eye Hospital in London and Oxford Eye Hospital in Oxford, said that six people have been treated thus far with no adverse effects. This therapy also uses an AAV2 to get copies of the healthy gene into the retinal cells.

Dr. MacLaren notes that all six patients entered the trial with relatively good vision, and the goal is to demonstrate that the treatment prevents vision loss. He estimates that it will take at least two years to determine if the patients’ treated retinas have less degeneration, and better vision, than their untreated retinas.

We need to keep in mind that these are very early results for just a handful of patients. Cautious optimism is in order. Not every treatment that enters a clinical trial will be a home run. But the progress is exciting, and we couldn’t have a better group of researchers on the front lines working to get these treatments out to the people who need them.

By the way, the Foundation funded critical lab studies that made both the choroideremia and MERTK gene therapy clinical trials possible.

Administered by an injection into the eye like that used for wet age-related macular degeneration (AMD), nanoceria are tiny manmade nanoparticles (1/12,000^th the diameter of a human hair) that literally devour the byproducts of oxidative stress that cause damage and vision loss in a variety of retinal diseases.

This team has now demonstrated nanoceria’s effectiveness in four different mouse models of retinal degeneration — adRP, Usher syndrome, wet AMD and degeneration caused by strong light exposure.

We are excited by the potential of this treatment approach for many of our retinal degenerative diseases, and that the OU team is working to bring it into the clinic. The team still has work to do in perfecting this treatment, but it’s making excellent progress.

Hats off to Dr. James McGinnis, who is leading this effort.

This is just one example of many we have seen at ARVO so far of how donations to the Foundation are yielding impressive returns.

This year’s theme is “Translational Research: Seeing the Possibilities,” which is fitting, seeing as the Foundation has its hand in several clinical, or human, trials aimed at eradicating blindness. In fact, FFB’s partnership stamp will be on roughly 140 abstracts and posters being presented at ARVO.

But I won’t only be there as a representative of the Foundation; I’ll be something of a student as I attend symposia, workshops and lectures and wend my way across the convention floor, taking note of the research posters and exhibitors. I also won’t be alone. Half a dozen members of FFB’s science team will be with me, covering every possible angle, including meetings with the Foundation’s research and corporate partners. So prepare yourself for a series of informative, behind-the-scenes posts next week, photos included. Just don’t expect me to come back with a tan.

Tel Aviv, Israel

Now that I’m back from my trip to Israel, I wanted to offer a couple more posts about my visit, the first covering a fascinating research conference in Tel Aviv.

While attending the Israeli meeting of the Association Research in Vision and Ophthalmology (ARVO), FFB Board member David Brint and I were immediately impressed by Israel’s cutting-edge genetic research. Scientists there are searching for a number of inherited retinal disease genes using state-of-the-art screening technologies and techniques. And the genes they’re after not only affect Israelis, Palestinians and others in the Middle East, but also people in the U.S. and around the world.

We were particularly impressed with Dr. Tamar Ben-Yosef, a knowledgeable and insightful young woman, whose laboratory at Technion University is on the hunt for genetic defects that cause retinitis pigmentosa (RP) and Usher syndrome. She is also working with newly identified RP genes — including MAK and DHDDS — to understand how defects in them cause vision loss. That information will be critical to the development of sight-saving treatments and cures.

Dr. Ben-Yosef told us about her challenging work in understanding an unusual form of RP that causes severe cone degeneration. (RP usually affects both types of photoreceptors, rods and cones, but rods more severely, at least initially.) What’s also unusual is that the disease-causing genetic mutation is found in multiple retinal cell types, including photoreceptors and ganglion cells.

David and I also saw presentations and posters from our good friend Dr. Dror Sharon, an FFB-funded researcher from Hadassah Medical Center, who is studying a number of genes, including CRB1, which is linked to about 10 percent of all Leber congenital amaurosis (LCA) cases in Israelis and Palestinians. In addition to previously discovering the RP gene FAM161A, he continues to investigate the way its affect on rods is different from its impact on cones. That work will ultimately lead to targets for treatments.

Lest anyone think that Hadassah and Technion have a lock on the genetics research in Israel, there were reports on LCA, Usher, different forms of RP (dominant and recessive) and achromatopsia (day blindness) from the Rabin Medical Center, Assaf Harofeh Medical Center, Edith Wolfson Medical Center, Tel Aviv University and Hebrew University School of Veterinary Medicine in Rehovot.

We also learned that age-related macular degeneration (AMD) affects individuals in Israel just like people elsewhere in the developed world, and, as a result, there’s a lot of research into the causes (genetic and non-genetic) and potential treatments. One particularly interesting finding from Dr. Itay Chowers’ group at Hadassah is that one of the primary genetic changes that increases dry AMD risk is found at a higher frequency in the Arabic population than in the Jewish population.

I must say, while the Israeli ARVO wasn’t quite the size of the annual ARVO  conference in the States, the quality of the research was outstanding. In addition to the great genetics work, the science community is also doing outstanding stem cell research, some of which I reported on in my previous post.

Before arriving at the conference, I was concerned about the potential language barrier. I knew that most of the talks were in Hebrew. But, fortunately, the slides and posters were in English. So, while my Hebrew (and David’s) is very rusty, I was able to understand the science, which was some of the best I’ve seen.

Photo courtesy of travelmania.com