Want to know about gene therapy? Our playlist features four videos, one each from four renowned researchers, including Dr. Eric Pierce, chairman of FFB’s Scientific Advisory Board, who does a great job summing up the vital role research plays in finding treatments and cures:

We also offer playlists covering stem cell therapy and gene discovery. And you won’t want to miss the video on why making donations to FFB’s research is so important at this crucial time:

To view all of the Foundation’s playlists, click here.

The CNTF caused the cones to deconstruct, regenerate and come back even stronger, so that they were able to transiently provide day vision. Specifically, the cones grew new and more robust outer segments, the antennae-like projections that process light to make vision possible.

The Pennsylvania team came up with this innovative approach because it was having problems with a gene therapy it had developed for achromatopsia caused by mutations in the CNGB3 gene. The therapy worked well in younger dogs, but not in canines older than one year. However, the injection of CNTF prior to the gene therapy proved to be an effective solution to the problem.

You may be asking: Will this restorative approach work for rods, the cells that provide night and peripheral vision, or other diseases, such as retinitis pigmentosa (RP)? Can photoreceptor deconstruction and regeneration be a new cross-cutting therapeutic approach?

While these are distinct possibilities, much more research is needed to determine CNTF’s potential. Deconstructing a photoreceptor to resurrect it is still scientifically bold. Before we move this type of therapy into humans, we want to have a reasonable level of confidence that photoreceptors will be regenerated by the process. It is also important to demonstrate that cone restoration can last longer than it currently is.

Those of you who have been following Foundation-funded research may already be familiar with CNTF. It’s the therapeutic protein delivered by Neurotech’s encapsulated cell technology (ECT), a tiny implantable device the size of a pencil head. But the amount of protein diffused by the ECT is a relatively low dose that is thought to be only protective; it isn’t enough for cone destruction and regeneration.

Results from clinical trials of ECT suggested that it was slowing vision loss for people with dry age-related macular degeneration. It also appeared to have a beneficial effect on retinal health for people with inherited retinal diseases such as RP and Usher syndrome.

Human studies of ECT continue. The Foundation is funding an imaging study of ECT at the University of California, San Francisco, to better understand its true potential for saving cones and vision. The National Eye Institute is also conducting an ECT clinical trial, interestingly enough, for people with achromatopsia, but as a protective therapy.

As I’ve said in previous blog posts, science is always full of surprises, and CNTF is a prime example. Its potential applications — in both low and high doses — are very intriguing.

One final observation: Whoever came up with the adage, “You can’t teach an old dog new tricks,” never met a researcher funded by the Foundation.

Pictured, above: an image of a retina, courtesy of Dr. Nicolás Cuenca, University of Alicante.

Ultimately, it is as important to design a good clinical trial as it is to develop a good treatment. We could have the best treatment ever devised, but without a good human study to demonstrate its safety and efficacy, we’ll never obtain U.S. Food and Drug Administration approval, to get it to the people who need it.

Designing a clinical trial for retinal disease therapies is challenging for many reasons. First, retinal diseases often progress slowly and affect vision in ways that are not easy to measure. Often, evaluating visual acuity by having someone read an eye chart doesn’t tell us if a treatment is actually saving vision. We may need to look at the person’s peripheral vision or ability to adapt to dark settings.

Observing structural changes in the retina itself may enable us to more quickly determine if a therapy is benefiting vision. Figuring out the best “outcome measures,” as we call them, for use in a clinical trial is one of the most important goals of ProgSTAR.

ProgSTAR will also help identify the best potential participants for a clinical trial of a Stargardt disease therapy. Will people with early-stage or late-stage disease be more likely to respond to a therapy?  How long will we need to monitor them to observe a response? We need answers to these questions to implement treatment studies that are cost-effective and expedient.

Not only do we need the right patients for a clinical trial; we need good clinical researchers. The Foundation has assembled the world’s best Stargardt disease experts for ProgSTAR. Led by Dr. Hendrik Scholl, of the Wilmer Eye Institute at Johns Hopkins, these investigators are unmatched in their understanding of Stargardt disease, and participation in the study will advance their knowledge even further. Dr. Patricia Zilliox, the Foundation’s chief drug development officer, serves as project director. She is well-qualified, with more than 30 years of industry experience.

ProgSTAR is monitoring approximately 200 people enrolled at nine clinical centers. They will be monitored for two years, but researchers are also looking at retrospective data on patients to get a better picture of how the disease and vision loss progress. ProgSTAR is a “by invitation-only” party; investigators are recruiting only their existing patients to participate.

It is rare for a non-profit foundation to fund a natural history study, because they are expensive — ProgSTAR will cost at least $3 million — and they don’t provide an immediate return of a new therapy. But, as I’ve just explained, these studies are invaluable for moving treatments forward for inherited retinal diseases; they bring us a big step closer to a cure.

Pictured, above: Dr. Hendrik Scholl conducts an electroretinogram, or ERG, with a patient at the Wilmer Eye Institute.

While essential to fighting blindness and many other conditions, translational research is painstaking and very expensive. It comes with risks and requires extensive clinical and regulatory expertise. It is no cake-walk.

But as the following video shows, Foundation-funded researchers developing a variety of treatments — including stem-cell, genetic and pharmaceutical therapies — are succeeding in meeting these challenges. Their determination and confidence are quite inspiring. Check out the video — I think you’ll agree.

In the Proceedings of the National Academy of Sciences, the investigators report sustained vision improvement of three years, thus far, in the treated eyes of participants. However, they also note that retinal degeneration, the loss of photoreceptors, continued in the treated eyes at a rate that was similar to untreated eyes.

Before I elaborate on the questions these results raise, it is important to be clear on what we do know from the LCA gene therapy human studies underway.

First, the Pennsylvania-Florida team has treated 15 patients, providing vision improvements without any serious adverse events. Establishing safety is the primary goal of this Phase I/II study, and, thus far, the team has done that.

Second, patients in the other gene therapy clinical trials for LCA, including the study at the Children’s Hospital of Philadelphia (CHOP), have also experienced vision improvements without serious adverse events. CHOP has also reported good results in the treatment of some patients’ second eyes. More than 40 people have been treated in six LCA gene therapy clinical trials.

The most important and immediate question is: Are the other LCA (RPE65) gene therapy clinical trials also observing loss of photoreceptors in the treated eyes of their patients? Their teams haven’t formally reported information on rates of degeneration, but I’m currently investigating this to learn what they do know at this juncture. If they aren’t seeing loss of photoreceptors, then we need to figure out why there are differences in retinal degeneration in treated eyes among the different studies.

If investigators at the other trials are observing continued retinal degeneration, it may mean that we need a more advanced form of gene therapy, to ensure that all of a patient’s photoreceptors are treated. Such a therapy might do a better job of slowing or stopping degeneration and preserving vision over a longer period of time.

Or, we may have to combine gene therapy with a drug or supplement that can stave off degeneration. These recent study results may also underscore the benefit of treating a patient early, before the degenerative process has time to gain momentum and becomes more difficult to stop.

I am very interested to see what will be observed in the early-stage gene therapy clinical trials underway for other retinal diseases. Thus far, we only have preliminary safety reports, so we’ll need to wait and see how these therapies impact both vision and retinal degeneration.

One of the big challenges in fighting blindness is the diversity of retinal degenerative diseases, and the likelihood that one approach to gene therapy will not work for all conditions. But the good news is that the retinal research community isn’t putting all of its eggs in one gene therapy basket.

As current gene therapy clinical trials move forward, and more are launched in the next two to three years, we’re going to learn a lot more about which approaches work well and which need refinement. I look forward to reporting additional information on these gene therapy studies as I get it.