Eye on the Cure

Dr. Richard Weleber

In leading the Foundation’s science program, an important part of my job is evaluating the work that our research centers are doing. To stay on top of the science, researchers send progress reports, we convene teleconferences and I also make site visits. Through these meetings and conversations, we discuss the investigators’ goals and challenges, and what we can do to help them succeed. With 131 grants at 73 institutions, staying on top of research progress is a big part of what my team and I do.

Dr. Patricia Zilliox, the Foundation’s chief drug development officer, and I visited the Oregon Health & Science University (OHSU) in Portland a couple weeks ago to meet with Dr. Richard Weleber and his team to discuss the status of their lab and clinical research. It was a highly productive and enjoyable visit. We spent much of our time discussing the status of current clinical trials and plans for future ones. It was wonderful to have Patricia join me, because she brings an enormous amount of experience and knowledge from her clinical development work with Alcon, a pharmaceutical company specializing in the eye. Her insights during the visit were invaluable.

If you didn’t know, OHSU is a world-class research and clinical facility, especially when it comes to human studies for inherited retinal degenerations. It’s a site for the StarGen™ gene therapy clinical trial for people with Stargardt disease and the UshStat® gene therapy for Usher syndrome type 1b. And OHSU will be a new site, later this year, for the Foundation’s valproic acid clinical trial for autosomal dominant retinitis pigmentosa. It currently serves as the collection and reading center for retinal images (photos of the retina, for example) and the valproic acid clinical trial.

To make all these human studies happen is no small feat, and Dick and his group do an incredible amount of heavy lifting to make them possible. From patient recruitment, to vision testing, to data collection and analysis, the workload is monumental. Furthermore, there are tight FDA regulations they need to adhere to along the way.

When I meet with Dick, I’m always impressed by his vast clinical knowledge of retinal diseases — more than 35 years’ worth — and the humility with which he disseminates it. He’s soft-spoken and friendly but, at the same time, direct, confident and eager to help. If he had the greenest lawn in your neighborhood, he’d not only tell you how he did it; he’d come over to your yard to help you make yours as green as possible. (For the record, I have never seen Dick’s lawn.)

One of the major topics of discussion during our trip was clinical trial endpoints. That is: What tests or measures do we use to determine if a treatment is working to save or restore vision? For diseases like retinitis pigmentosa, a simple eye chart often won’t suffice. We might need to measure peripheral or side vision, or, perhaps, sensitivity to light, or the ability of a patient to adapt to darkness. Selecting these endpoints is challenging but critical to determining the effectiveness of a potential treatment. We could have a great drug, but if we aren’t measuring the right outcomes, the trial results won’t enable us to get FDA approval.

Having examined and studied the retinas and vision of several thousands of people with retinal disease, Dick is an invaluable resource in determining which endpoints will work best for each disease and potential treatment. During our visit, he gave us insights into clinical trial endpoints for Stargardt disease, which can cause patchy and hard-to-predict patterns of vision loss. We also talked about possible endpoints for optogenetic treatments, which harness ganglion cells for vision. It’s an entirely new way of possibly restoring vision, so we need to make sure we get the outcome measures for that study right.

During the trip, we also met with Dr. Mark Pennesi, a bright young researcher and physician working with and learning from Dick. He’s a recipient of a Foundation Career Development Award, which the Foundation provides to attract new people into the world of inherited retinal disease clinical research. It’s critical that we have a good supply of clinical researchers to conduct human trials and provide patient care. Mark follows in Dick’s footsteps — he’s mild-mannered, but, from what I hear from patients who have seen him, he’s knowledgeable and willing to spend the time to explain what he finds and in terms that a non-scientist can understand. This is crucial to great patient care and something FFB is fostering in our clinicians.

Next month, I am off to Israel to learn about some exciting research efforts for a variety of inherited rare retinal degenerations. More to come on this.

Stay tuned to Eye on the Cure for more stories from the road.