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.

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.

Stem cells can also be used to protect existing photoreceptors by providing the sustained release of beneficial proteins. That is, the transplanted cells can act like a therapy factory built adjacent to the retina.

But stem cells are a two-edged sword. Researchers must carefully harness their power to ensure positive consequences. There are two primary safety concerns with emerging stem cell therapies:

• the development of tumors or other unwanted types of cells
• immunological reactions to the cells when they are transplanted into the eye

While it’s great that stem cells can form any cell type in the body, it’s also a little scary. Scientists need to make sure that a retinal treatment, for example, contains only retinal cells. The worst-case scenario would be that they develop into tumors.

Retinal researchers use proteins to tweak stem cells so that they differentiate into retinal cells or other desired cell types. When they produce stem cells lines, they employ what are fittingly known as Good Manufacturing Practices, or GMP, to ensure that the cells are as pure as possible.

When it comes to preventing an immune reaction to transplanted cells, there is some good news. The eye is considered “immune-privileged,” meaning it’s less susceptible to an attack from the body’s powerful immune system. A barrier comprised of blood vessels outside of the retina is what provides protection. This doesn’t mean there is no risk of an immune reaction — it’s just less than for transplants of other tissues and organs.

While stem cells come from a variety of sources, scientists are particularly excited about induced pluripotent stem cells (iPSC), which are derived from a patient’s mature cells, such as skin or blood. Because the patient serves as his or her own stem cell donor with iPSC, there is less chance of an immune reaction.

At the same time, researchers need to turn a few genes on and off to control which direction cells move in the developmental process. Using proteins to switch these genes on and off, researchers can control whether a cell moves backward in the development process, i.e., a skin cell reverts back to a stem cell state, or a cell moves forward, i.e., a stem cell becomes retinal. This tweaking of genes makes scientists a little nervous about the safety and stability of iPSC, because in some cases it has introduced new mutations. They have wondered if those mutations might cause an immune reaction.

However, a recent report in the prominent science journal Nature has quelled those fears. A Japanese team of researchers found “negligible immunogenicity” of mature cells derived from iPSC and embryonic stem cells.

The first clinical trials of retinal treatments derived from stem cells are being conducted by Advanced Cell Technology (ACT) and StemCells, Inc. The cells used in these therapies are designed primarily to play a protective role in the retina. ACT has reported safety and some modest vision improvement for people with dry age-related macular degeneration (AMD) and Stargardt disease. No reports have come out yet for StemCells, Inc.’s study for people with dry AMD.

The company ReNeuron is tentatively planning to launch its clinical trial of stem cells for people with RP in late 2013.

More stem cell clinical trials for retinal diseases are planned in the coming two to three years, so stay tuned. It is an exciting time in this high-potential field of research.

Pictured above: An enlarged image of stem cells.

The orphan designation was the result of the Orphan Drug Act of 1983, which facilitates the development of treatments for diseases affecting fewer than 200,000 people in the United States. Congress passed the act because markets are small for rare conditions, and companies are often not motivated to develop therapies for them.

Orphan status is granted by the U.S. Food and Drug Administration. The European Medicines Agency provides similar benefits for rare-disease therapies being developed in Europe.

Most emerging therapies in clinical trials for inherited retinal diseases have received orphan status, including Oxford BioMedica’s gene therapies for Stargardt disease and Usher syndrome type 1B and Advanced Cell Technology’s stem cell treatment for Stargardt disease.

I am always quick to point out the irony that rare diseases aren’t all that rare. As I mentioned in a blog post on Rare Disease Day — February 29, 2102 — there are more than 7,000 rare diseases, and one in 10 Americans is affected by one. Chances are that you or someone you know is affected by a rare disease, and will someday benefit from orphan-designated therapies.