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.

So why can diagnoses be tough to come by? First and foremost, most eye doctors don’t see many patients affected by inherited retinal diseases, because the conditions are rare. They simply don’t have familiarity with them, even if they learned about them in medical school and during their residency training.

Another major reason diagnoses are tough is that some conditions can look the same to even a well-trained retinal specialist. For example, cone-rod dystrophy affects the macula, the central region of the retina, much in the same way that Stargardt disease does. X-linked retinitis pigmentosa (XLRP) and choroideremia can look similar in appearance. Sometimes it isn’t clear upon examination whether a young child has retinitis pigmentosa or a form of Leber congenital amaurosis.

Also, diseases don’t always behave the way experts expect them to. XLRP is a great example of this phenomenon. According to textbooks, XLRP only affects men; females are unaffected carriers. But in recent years, researchers have found that a surprising number of women have vision loss, sometimes severe, from XLRP.

Despite these challenges, there are things you can do to improve your chances of getting an accurate diagnosis:

Visit a Clinician at a Retinal Research Center
Academic research institutions are where most experts in inherited retinal diseases practice, and FFB funds many of them. Known as “clinician-researchers,” they have the most knowledge and the best tools to make diagnoses.

These centers are located in many major cities in the United States, Europe and Asia. While it can be financially and logistically difficult for some patients to visit these centers regularly, even one visit can make a world of difference in understanding a disease.

Contact the Foundation at 1-800-683-5555 or info@FightBlindness.org to find the research center most convenient for you. We also maintain a list of privately practicing retinal doctors who are knowledgeable about inherited retinal degenerations.

Get Genetically Tested
Finding the disease-causing gene is the key to making a definitive diagnosis. If you find the genetic defect, you have the answer. Furthermore, finding the gene can position you for clinical trials of emerging treatments.

Of course, the genetic-testing process can be a real bear. That’s because only about 45 percent of the genes that cause these diseases are known, and the discovery of new genes is a research effort that can take many years. It isn’t like getting your cholesterol checked at your local doctor’s office or lab — you won’t get an answer right away, and sometimes you won’t get an answer for years until the gene is identified during research.

Also, it is best to contact a specific research center, and potentially its genetic counselor, to get a genetic test. The Foundation has online genetic testing resources, and the company InformedDNA offers fee-based, genetic counseling services over the phone for people with inherited retinal diseases.

Be Persistent and Tenacious
I can’t say enough how important it is to advocate for one’s self in getting answers to questions about a diagnosis or genetic test results. While people might not always get the answers they want — e.g., “We can’t find your gene” — they should get an answer. At the end of the day, they must make the follow-up calls to get the information to better understand a condition and how to deal with it.

For those who do jump through all these hoops and can’t get a definite diagnosis, there is good news. The Foundation funds several emerging treatments — including drugs, gene therapies and stem cell treatments — that are designed to work for people with a wide range of diagnoses.

Many of these potential therapies are funded through our Translational Research Acceleration Program and positioned to move into human studies within the next few years.

Finally, the Foundation is funding a number of outstanding researchers, who, thanks to advancing technology, are continually improving their ability to find disease-causing genes and make diagnoses.

Clearly, there continue to be formidable challenges for doctors, researchers and patients, but we are getting more answers to inherited retinal diseases every day.

Photo: Courtesy of National Eye Institute

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.

With a population of about 17,000, Beaver Dam, Wisconsin, is a typical Midwestern community and, according to its website, “a thriving city and wonderful place to call home.” With attractions such as the beautiful 6,000-acre Beaver Dam Lake and the Midwest Cream Cheese Competition, who am I to argue? But most important, at least in the fight against blindness, Beaver Dam plays a big role in the search for knowledge about age-related macular degeneration (AMD).

Launched in 1987 by the University of Wisconsin-Madison, and funded by the National Eye Institute, the Beaver Dam Eye Study has been collecting prevalence, incidence, and risk factor data for age-related eye disease, including AMD, with the goal of better understanding the conditions. About 5,000 of Beaver Dam’s 6,000 citizens aged 43 through 80 were originally enrolled in the study, which has been tracking eye disease in five-year increments.

According to Dr. Ronald Klein, a University of Wisconsin physician-researcher involved in the study, Beaver Dam was selected as the site because the city’s residents had been highly reliable participants in prior studies.

One important observation from the study on AMD genetics was recently reported by Dr. Klein in the Archives of Ophthalmology. He and his colleagues determined that 80 percent of people who had high genetic risk factors did not get late AMD, the stage of the disease associated with significant vision loss, by the age of 80. In other words, genetics is ultimately not a good predictor of who will get late AMD. However, information on genetics does help researchers better understand the disease and identify targets for treatments.

Dr. Klein says that the best way to determine if you are at risk of getting late AMD is through regular visits to your eye doctor. By examining your retina, he or she can identify the deposits known as drusen, which put you at risk for late AMD and associated vision loss.

Drusen usually start appearing long before the disease is advanced. When the drusen become large, they’re associated with increased risk of progression to late disease.

The best thing you can do to minimize your AMD risk is to not smoke. Eating lots of fruits and vegetables, maintaining a healthy weight, getting exercise and protecting your eyes in bright sunlight may also help minimize AMD risk.

Does that mean you shouldn’t occasionally enjoy a piece of cake like the one pictured above form the Midwest Cream Cheese Competition? No. The operative words here are: “a piece” and “occasionally.” But that sure does look like “Dam” good cheesecake.

Pictured, above: “Checkers,” an entry in the 2011 Midwest Cream Cheese Competition.