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:

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:

Up through the age of 7, as The New York Times pointed out, Corey Haas, a New York state resident, was living virtually blind. A rare disease called Leber congenital amaurosis (LCA) had rendered him legally blind at birth, and he had since been forced to use a cane and learn to read Braille. Although he was attending his local school, where he received special-needs assistance, he wasn’t able to do what many boys that age can – play sports, ride a bike or see the blackboard.

But just after his 8^th birthday – as part of a clinical, or human, trial taking place worldwide – Corey was given a gene therapy treatment in one eye that, over the next year, would improve his vision significantly. By the age of 9, he was navigating a once-impassible obstacle course, reading large-print books and playing Little League baseball. His parents, Nancy and Ethan, were understandably overjoyed, as previously they’d watched Corey’s eyesight steadily degenerate.

The clinical trial, conducted in part by Dr. Jean Bennett at The Children’s Hospital of Philadelphia, is funded by the Foundation Fighting Blindness. It, along with similar trials for LCA gene therapy, is ongoing, as it takes a few stages, over as many years, to prove that a treatment is both safe and effective. The latest good news, which Bill Schmidt included in his post, is that treatments of the participant’s second eyes, including Corey’s, have been successful thus far.

Over the last four decades, FFB has raised more than $500 million, and Corey’s story serves as a case study for what we are working so hard to accomplish – curing blindness. With this particular form of LCA, as with many diseases, the Foundation has been involved in every step of the process.

FFB funding enabled researchers to find the genetic defect causing the condition and conduct the pre-clinical work necessary to better understand the disease and develop a potential treatment deemed safe enough to administer to humans. Foundation funding was then used to execute clinical trials which have restored vision and improved the lives of Corey and roughly 40 other people affected by that specific form of LCA.

But tens of millions more – people with diseases like retinitis pigmentosa, Stargardt disease, Usher syndrome and age-related macular degeneration – are also seeking treatments.. Gene therapy clinical trials are either underway or on the horizon for each of these diseases and more, which is why the Foundation is asking people like you to donate to our “Light the Way to a Cure” holiday fundraising campaign. No donation is too small or large, and each supports our efforts to end blindness for those with retinal diseases.

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