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:

At the age of 80, Dick Coulson (featured earlier this year in The New York Times) resides in Lakewood, Colorado, where he gets around with a white cane and engages in his favorite pastime, photography. Twenty-five years ago, during a routine eye exam, the doctor noticed yellow spots, otherwise known as drusen, on Dick’s retina, an early sign of AMD. Over the next 15 years, Dick’s sight got progressively worse, forcing him to give up driving and his orthodontic practice. He’s now legally blind.

Dick’s not a complainer. He’s still an active photographer, using a digital camera to shoot, then a magnifier on his computer screen to select images. And he loves to travel, even if that means asking strangers to help him find the gates for flights. Like most Foundation Fighting Blindness members, Dick also keeps up with the latest research for treatments for AMD and other retinal diseases.

As the Foundation’s CEO, Bill Schmidt, pointed out in his blog post listing the top 12 retinal-research advancements of 2012, StemCells, Inc., launched a clinical trial – one that involves human participants – for a treatment of AMD this past summer. In addition, two participants in another stem-cell-related clinical trial, this one conducted by Advanced Cell Technology (ACT), demonstrated improved vision this past year. One has AMD, the other a juvenile form called Stargardt disease.

Stem-cell-based therapies – including those derived from a patient’s blood or skin – are among the many cutting-edge approaches to treatments the Foundation has funded for decades. The $500 million we’ve raised thus far has been funneled into both pre-clinical and clinical research, for potential gene therapy and pharmaceutical treatments as well. Considering that 10 million Americans are affected by retinal diseases – including retinitis pigmentosa, Usher syndrome and choroideremia – we’re dedicated to funding the best researchers in the most prestigious institutions worldwide.

Which brings me back to Dick Coulson. As resourceful, energetic and optimistic as he is, he supports the Foundation’s work,  to ensure that people entering their post-retirement years – that’s you, Baby Boomers – don’t have to lose their vision to AMD. The Foundation’s “Light the Way to a Cure” fundraising campaign, which doubles every dollar donated, will help us keep the research momentum going. And that will lead to treatments and cures, sooner rather than later.

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

But for a moment, as we put the wraps on 2012, it is very inspiring to look back on the past year and reflect on the many exciting advancements that have been made in our quest for treatments and cures.

Thanks to the scientific community and everyone else working to bring an end to retinal diseases, our strides have been incredible. Thanks to our success, we have more momentum than ever before as we move into 2013.

Here is my alphabetical list of the Top 12 Retinal Research Advances for 2012:

1.  Argus II “Bionic Retina” Receives Recommendation for FDA Approval 
2. Choroideremia, RP Gene Therapies Perform Well in Early Clinical Trials 
3. Foundation Commits $2 Million to Develop MitoChem’s Cross-Cutting Drug 
4. Gene Therapies for Stargardt Disease and Wet AMD Safe Thus Far in Clinical Trials 
5. Omega-3 Rich Diet Combined with Vitamin A Slows Visual Acuity Decline in RP 
6. Patients’ Skin Cells Help Researchers Move Closer to Treatments for Best Disease 
7. Positive Results for Second Eyes Treatment in LCA Gene Therapy Clinical Trial 
8. ProgStar: Natural History Study for Stargardt Disease to Help Prepare for Clinical Trials 
9. QLT’s Drug for RP and LCA Performs Well in Clinical Trials 
10. StemCells, Inc. Launches Clinical Trial for Dry AMD 
11. Two Participants in ACT’s Stem Cell Clinical Trial Show Improved Vision 
12. Usher Syndrome Gene Therapy Clinical Trial Begins, Safe Thus Far in Three Patients

I would be remiss if I didn’t mention that these amazing advancements were made possible by donations from charitable individuals and organizations focused on finding treatments and cures for blinding diseases. In the spirit of the holidays, and as part of our end-of-year “Light the Way to a Cure” campaign, an FFB benefactor is matching every dollar donated to the Foundation during the month of December. Your support — this month in particular — will help to ensure that we have a similar list of accomplishments to report this time next year. I wish you a safe and joyful holiday season, and I look forward to working with everyone associated with the Foundation to make 2013 an even brighter year in our drive for sight-saving treatments and cures.

With that in mind, I’d like to share an extraordinary essay written by Colin Krouse, a 15-year-old from Wayne, Pennsylvania, whose 13-year-old brother, Casey, has Stargardt disease.  This fall, the Krouse family participated in the 6^th annual Philadelphia VisionWalk, a 5K fundraiser, and in his essay, Colin shares what it’s like to be the sibling of someone with a retinal disease. He also thanks his brother for reasons you’ll read below:

Four years ago, my family was seated in our living room, watching Sunday night football. It was not an uncommon sight, except something was a bit off. Throughout the night, my parents made comments about my little brother, Casey, who was inching closer and closer to the TV, squinting as if it were the middle of a bright, sunny day. We didn’t think much of it at first, but as this kept occurring, it was obvious that this was something that should probably get checked out.

Casey went through numerous tests and saw a countless number of doctors who all said the same thing – they couldn’t figure out what was wrong. More than two years later, Casey was finally diagnosed with Stargardt disease, which progressively worsens central vision. Imagine a big black dot in the center of each eye that grows larger every day. That’s basically what Stargardt is.

The news didn’t affect me at first, mostly because I didn’t understand what was going on. But, as I became more curious, I began to feel the impact of Casey’s situation. Suddenly, thoughts were flying through my mind. It felt like I had literally lost my best friend. If I had a brother who couldn’t see, who would I play one-on-one baseball with in the backyard? Who would I play video games with? Or ride bikes with down the street to the park?

It was selfish of me, but, initially, I resented my little brother. I was angry, not at him but the situation. It was an anger that could have been soothed by talking to someone, but who was there to talk to? No one was there when I blasted one of his sloppy change-up pitches into the apple tree and trotted around the bases while being pelted with Casey’s glove and shoes. No one was there when, once again, he beat me in basketball, and I threw the ball at him, sending him inside screaming and bragging at the same time. No one was there when we made up after another one of these fights by sneaking freeze-pops and eating them together in the garage.

No one could possibly understand the bond that my brother and I shared, so who could possibly empathize with me? It took a while to realize that the situation was not a burden, but rather a blessing. Over time, as I saw Casey still strike everybody out, best everyone in the classroom and continue to land his patented hook shot over my head, I realized he wasn’t slowing down.

At that point, I began to learn from my little brother. I learned perseverance as I saw him swing at and miss yet another pitch, only to rip one into the gap when it mattered most. I learned courage as, on the basketball court, he took on kids twice his size before nailing a jump shot. I learned determination as he overcame his struggles to read words and see numbers to still get that A-plus.

Best of all, this past summer, I watched Casey – the same kid who had tested as legally blind just a few weeks earlier – pitch a complete game against the number three team in the nation at the Aberdeen, Maryland, baseball complex and send his team of underdogs into the semifinals of the tournament.

I now realize how much I’ve benefited from having Casey in my life. I couldn’t ask for a better little brother, who is still my toughest competitor. I love him more than anyone else in the world, including me. Of course we still have our tiffs, but, at the end of each day, I can’t help but think of how lucky and thankful I am to have him in my life.

– Colin Krouse

Pictured, above: Colin (left) and Casey Krouse at the Philadelphia VisionWalk.