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:

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.

Medical research is a monumentally expensive endeavor that demands investment from nonprofits like the Foundation Fighting Blindness as well as biotech companies and the federal government. It’s a team effort which, in the past, has resulted in a cure for polio and drugs enabling those diagnosed with AIDS to live full and productive lives. Those are just two of innumerable examples.

Not only would the “fiscal cliff” adversely impact long-term public health; it would allow the United States to fall behind other countries and lose valuable time battling diseases such as Alzheimer’s, Parkinson’s, muscular dystrophy and the many retinal degenerations the Foundation has fought, for more than four decades, to eradicate.

That’s why FFB and more than 50 other health-related nonprofits will join Research!America in its “Save Research” campaign November 12-16. Along with our partners, we will raise public awareness and lobby Congress to change its mind before the January 1st deadline.

To find out how you can aid the Foundation in this effort, check out our “We Need Cures, Not Cuts!” web page, which offers guidance on raising awareness, including through social media. I also encourage you to email President Obama and your local members of Congress directly, which you can do with help from our advocacy tool.

So, what does the “fiscal cliff” mean to those with vision-robbing retinal diseases? Worst-case scenario, the National Institutes of Health (NIH), the world’s largest biomedical research agency, and the National Eye Institute (NEI), the part of the NIH that funds vision research, would face significant cuts in funding. The NIH stands to lose up to $4 billion, the NEI $55 million, if Congress fails to act by the end of 2012.

Clearly, the stakes are high for vision research. Even if Congress does act, it is likely that a longer-term debt reduction plan will be negotiated next year that could negatively impact biomedical research funding generally.

Bill Schmidt, CEO of the Foundation Fighting Blindness

So we all need to remain vigilant in our efforts to ensure that legislators understand the importance of federal investment in research and protect it as a budget priority. The reality is that basic research is not something the private sector can, or will, invest in if public support erodes. As numerous studies have shown, this public investment also leads to the creation of jobs in our biotechnology and pharmaceutical sectors.

So I encourage you to join us and the Research!America alliance next week in engaging with your federal elected officials to ensure that biomedical research funding remains a priority in the federal budget.

Usher syndrome type 1 occurs if any of these proteins are missing or defective. However, normal mice have neither the girdle nor the abundance of Usher 1 proteins in that region of their photoreceptors, making them an inadequate model of human Usher 1 disease.

Traditionally, testing emerging therapies in animal models has been an important first step before evaluating them in humans. As the Usher 1 mouse illustrates, animal models have their limitations.

The answer to this problem, as the French researchers note, may be induced pluripotent stem cells (iPSC). Scientists have found a way to take a small skin or blood sample from a patient, turn back the clock on those sample cells so they become stem cells, and then coax them forward to become photoreceptors, or any other cell type in the body. And voila! — we have a model of human retinal disease that we can study in a dish. We can even use the new cells to test drugs and gene therapies.

Keep in mind that iPSC won’t be a complete replacement for an animal model; we still need a complete biological system for testing safety. But human iPSC greatly improve our ability to understand disease and test potential therapies.

What’s even more exciting is that researchers are using induced pluripotent stem calls to make new photoreceptors and other retinal cells, which can be transplanted back into the patient to replace those cells lost to retinal disease.

The therapeutic potential for iPSC is so big, a Japanese researcher just won a Nobel Prize for discovering them.

Above: detail image of a retina, with photoreceptors in green.