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.

What’s signficant about many emerging neuroprotective therapies for the retina is that they have the potential to treat a wide range of diseases, regardless of the genetic mutation causing vision loss. With about 200 genes linked to retinal diseases, this is a huge plus. They might also be used in conjunction with a genetic therapy to enhance its vision-saving effects.

Though neuroprotection usually isn’t addressing the root cause of the disease, it may be nearly as beneficial as a permanent fix, if useful vision can be saved for a person’s lifetime.

Neuroprotective treatments are being developed in many forms — proteins, drugs (small molecules) and nutrients. And there are several ways to get a neuroprotective therapy to the retina, including eye drops and oral medications.

Imagine having a therapy factory in the retina — in the forms of transplanted cells or genes — that provides continual release of neuroprotective proteins. Well, researchers are working on those, too.

Here are three examples of emerging neuroprotective therapies for the retina:

Protecting Mitochondria — MitoChem Therapeutics, a Foundation-funded  start-up company, has identified two compounds, which show potential for saving vision for people affected by several retinal diseases, including retinitis pigmentosa (RP), cone-rod dystrophy, Bardet-Biedl syndrome, Usher syndrome, Stargardt disease and age-related macular degeneration (AMD).

The compounds work by protecting mitochondria, the power supplies for all cells in the body, including those in the retina. Investigators have refined the compounds to the point where they save virtually all of the photoreceptors in a mouse model of retinal degeneration. They’ve also demonstrated that eye drops can effectively deliver large amounts of one compound to retinas in eyes comparable in size to those in humans. Eye drops are beneficial, because they minimize potential systemic side effects.

Docosahexaenoic Acid (DHA) — DHA is an important structural component of cells in the brain and the retina. It appears to have many neuroprotective properties and is prescribed for a variety of conditions, including heart disease. Perhaps most relevant to retinal degenerative diseases, DHA can reduce the destructive effects of inflammation and oxidative stress. It also helps maintain the structure and metabolism of photoreceptors.

The Retina Foundation of the Southwest is completing a Foundation-funded clinical study of DHA for males with X-linked RP. Previous clinical studies conducted by Dr. Eliot Berson show that vitamin A combined with DHA can slow vision loss in people with RP. In 2014, the National Eye Institute will complete a clinical study of DHA and other nutrients for people at risk of advanced AMD. DHA can be obtained by eating salmon, tuna and other coldwater fish, or by taking fish-oil or algae supplements.

Rod-Derived Cone Viability Factor (RdCVF) — Drs. José Sahel and Thierry Léveillard, of the Institut de la Vision in Paris, received the Foundation’s Trustee Award for their discovery of Rod-derived Cone Viability Factor (RdCVF), a protein that preserves and rescues cones, the cells in the retina that provide central and color vision. They are now developing a gene therapy that provides sustained delivery of RdCVF after a single treatment. The protein could be beneficial to people affected by a broad range of retinal diseases, including several forms of retinitis pigmentosa. With Foundation funding, the researchers are working to move their RdCVF gene therapy into a clinical trial.

There are several other emerging neuroprotective therapies in the Foundation’s research portfolio. Stay tuned to Eye on the Cure and the Foundation’s website for updates on these emerging cross-cutting treatments.

Pictured, above: Some neuroprotective therapies may be delivered by eye drops. (Photo courtesy of the National 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.

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.

Photo courtesy of the National Eye Institute

I am always excited when a new research paper comes across my desk reporting on an emerging treatment that has saved or restored vision in an animal or cell-based model of retinal disease. The advancement provides meaningful hope for a therapy that can benefit people. But it raises a big question for the Foundation Fighting Blindness: What will it take to move the treatment into and through human studies?

Moving a potential vision-saving treatment out of the laboratory and into a clinical trial – which, in the United States, must be authorized by the U.S. Food and Drug Administration (FDA) – is a risky and costly proposition. While it can cost hundreds of thousands of dollars to demonstrate that a potential treatment works in an initial rodent or other model of retinal disease, it costs millions to “translate” it into a human study. And even when the investment is made, it may not yield the return of an FDA-approved therapy.

Why is translational research so expensive?

Ensuring safety is a big reason. A therapy must be carefully evaluated in additional animal and/or cell-based models to show that it causes no adverse problems – for example, triggering an immune reaction or having a toxic effect. Also, because the human eye is much bigger than a mouse eye, researchers need to demonstrate that they can get a therapeutic dose of the treatment to the retina through eye drops or orally. The latter exposes the rest of the body to potential systemic side effects.

In addition, researchers must produce a treatment that follows “good manufacturing practices,” or GMP, to ensure that it is sterile and safe, and that each dose consistently delivers the same concentration of drug or biological therapy.

And finally, for the clinical trial itself, there is the recruitment of patients, the selection of clinical researchers and trial sites and the determination of the protocol to be followed with outcome measures that define success. All of these efforts and decisions must be documented meticulously to gain authorization from the FDA in the United States or equivalent agencies abroad to launch a human study.

Perhaps the most sobering aspect of translational research is that, even if all of the above are done correctly, there is no guarantee that the proposed therapy will ultimately save or restore vision in humans. In fact, most potential treatments won’t make it through the clinical trial process.

Because large pharmaceutical companies and therapy developers are often reluctant to take on the significant risk and expense of the translational process, many potential therapies stall in what the drug industry refers to as “The Valley of Death.”

While the reality of translational research can seem overwhelming, the Foundation Fighting Blindness is taking the challenge head-on through its Translational Research Acceleration Program (TRAP). By advancing therapies into early-stage clinical trials, the program is also “de-risking” the treatment development process to attract for-profit and venture capital investments. The good news: Some TRAP projects are already doing just that.

The program was established by Gordon Gund, co-founder and chairman of the Foundation, along with other key research investors, who recognize that the focus on translation is imperative to get vision-saving therapies out to the millions who need them.

Launched in 2008, the program is investing $20 million annually in moving promising gene therapies, stem cell treatments and pharmaceuticals through late-stage lab studies and into clinical trials. TRAP also supports projects for genetic testing, the discovery of new disease-causing genes and imaging studies to better understand retinal disease processes and treatment effectiveness.

It is important to note that while some TRAP projects target specific diseases, several of the efforts have the potential to benefit people affected by a wide range of conditions and independent of the genetic defect causing vision loss.

Fifteen projects are currently funded by TRAP. I encourage you to read more about them in this recent article on the Foundation’s website. As you will see, many are designed to move emerging therapies into clinic trials with the next two to four years.

With that in mind, I would also ask you to consider donating to FFB’s “Light the Way to a Cure” holiday fundraising campaign, where every dollar you donate through December 31 will be matched. Your money will go toward projects with strong sight-saving potential.

Donate to FFB’s “Light the Way to a Cure” Campaign: