The findings reported in a recent research paper from the University of Utah on autosomal dominant Stargardt disease are a great case in point. But before I discuss the new research, which was funded by the Foundation Fighting Blindness, let me give you a little background on this story. One word of warning – as my professional vernacular is loaded with acronyms, I’ll be serving alphabet soup with this post.

Stargardt disease affects approximately 30,000 people in the United States and 40,000 in Europe. A vast majority of the cases, about 95 percent, are autosomal recessive and mainly caused by mutations in the ABCA4 gene.

The other five percent are autosomal dominant, most of which are caused by defects in the gene ELOVL4. This form of disease is often referred to as STGD3. The University of Utah paper is specifically about new findings for ELOVL4 mutations.

In 2001, Foundation-funded researchers found that ELOVL4 was linked to STGD3. They also knew that ELOVL4 was involved in the production of very long chain polyunsaturated fatty acids (VLC-PUFAs), and suspected that a lack of those fatty acids was detrimental to retinal health. Humans get VLC-PUFAs by consuming their precursors, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are abundant in coldwater fish, as well as fish-oil and algal supplements.

In 2007, the University of Utah’s Dr. Paul Bernstein began a clinical trial of DHA and EPA supplementation for people with STGD3 to see if it would slow their vision loss. His observations of a Utah family with ELOVL4 mutations suggest that DHA and EPA supplementation might do so. In 2006, his group published a retrospective analysis, which found that the family members who had most EPA and DHA in their diets had the mildest retinal changes.

But alas, as we seem to be on a logical path forward for treating STGD3, a team of scientists from the University of Utah — which included Drs. David Krizaj, Peter Barabas and Bernstein — found that mice lacking VLC-PUFAs in their photoreceptors did not have retinal degeneration or associated vision loss. It appears to be a classic “one-step back” moment.

Now, these findings come with a major caveat (not to be confused with caviar, which, interestingly, is high in DHA and EPA). This new research is based on mouse models, which are by no means perfect replications of human STGD3.

However, the new study also suggests that ELOVL4 may be involved in something more than the production of VLC-PUFAs, and that “something” may also be linked to STGD3. More Foundation-funded research is underway to get a better picture of what causes STGD3.

Ultimately, Dr. Bernstein’s prospective clinical trial, which will conclude later in 2013, will tell us more about the role of DHA and EPA in STGD3.

In the meantime, comrades, I encourage you to check out my previous blog post on DHA and EPA, which discusses how these healthy fats have exciting potential for treating a wide range of retinal degenerations and other health conditions.

Pictured, above: Dr. David Krizaj (Photo courtesy of Dr. Bryan Jones, retinal neuroscientist at the University of Utah.)

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.

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.

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