Today’s Science, Tomorrow’s Breakthroughs

• Researchers supported by the Foundation have identified over 85% of the more than 200 genes known to cause retinal degenerative diseases.
• Foundation-funded researchers have linked variations in three genes to as many as 74% of all cases of age-related macular degeneration.
• With funding from the Foundation, investigators at the Universities of Texas, Michigan, and California, San Diego, Harvard Medical School, The Radboud University Nijmegen Medical Centre in the Netherlands, and at the Hadassah Medical Center in Jerusalem, Israel have discovered new retinitis pigmentosa-causing genes and gene mutations over the last year.
• Using advanced gene mapping technology, a Foundation-funded researcher at the University of Iowa is gathering data from 800 people with age-related macular degeneration.   This research is directly leading to an understanding of gene-disease relationships and identifying patients who share the same gene mutations and disease characteristics who could participate in upcoming clinical trials.

The concept is simple, but the impact is extremely powerful.  Through gene therapy, Foundation researchers replace damaged genes by delivering normal genes that can “replace” the genetically caused malfunctions that are responsible for retinal diseases.  This area of research holds significant promise for treating numerous inherited retinal diseases.

Leber Congenital Amaurosis Gene Therapy Clinical Study
Status: Ongoing Clinical Trial
Future Impact On: All Retinal Diseases

The ongoing human clinical trials using gene therapy to treat Leber congenital amaurosis, a severe form of retinitis pigmentosa in children, continue to yield exciting results.  More than 20 people participating in the trial show sustained improvement in vision.  Additional patients have been recruited for these trials and additional studies are being planned.  These successes are paving the way for developing gene therapies to treat a variety of retinal degenerative diseases.

Leber Congenital Amaurosis Gene Therapy
Status: Moving Toward Clinical Trial
Future Impact On: All Retinal Diseases

Foundation-funded researchers at the University of Oklahoma in collaboration with a biotech company, Copernicus Therapeutics, Inc., used a newly developed gene therapy protocol to successfully restore retina function in mice with Leber congenital amaurosis. This cutting edge approach links normal genes to very small particles that deliver them to the retina.  This is a significant advance over the current technology that relies on modified viruses to deliver therapeutic genes.  By using very small nanoparticles instead of a virus, there is less risk of triggering the body’s natural immune response to the gene delivery vehicle.  Nanoparticles have the potential to deliver much larger genes. This new approach was safely used in a clinical trial for cystic fibrosis, suggesting that the procedure may soon be ready for evaluation in human clinical studies for retinal degenerations.

Retinitis Pigmentosa Gene Therapy
Status: Moving Toward Clinical Trial
Future Impact On: All Retinal Diseases

A partnership between the Foundation and an Irish biopharmaceutical company, Genable Technologies, Ltd., is paving the way for the development of a gene therapy for dominant forms of retinitis pigmentosa.  Scientists are using advanced technology to shut down the gene that causes progressive vision loss in dominant RP, while simultaneously delivering a new, normal gene to the retina.  A clinical trial of the treatment could start as early as 2011.

Stargardt Disease/Cross-Cutting Gene Therapy
Status: Clinical Trials to Begin in 2010
Future Impact On: All Retinal Diseases

With Foundation funding, researchers and Oxford BioMedica have studies underway to find a delivery mechanism (known as a “vector”) for normal, large genes that impact vision loss.  Though this advance will be applicable to gene therapy for many diseases in the future, this Stargardt’s disease study is expected to move into clinical trials by the end of 2010 in Foundation-supported Centers.  Clinical trials on Usher syndrome and age-related macular degeneration are also likely within the next few years.  Oxford BioMedica has already cleared a major hurdle; recently when they received orphan designation from the Committee for Orphan Medicinal Products of the European Medicines Agency, which functions like the FDA, for the Usher 1b gene therapy project and received favorable review at the French regulatory commission for their Stargardt’s project.

Choroideremia Gene Therapy
Status: Initial Phase of Research Ongoing
Future Impact On: All Retinal Diseases

At Imperial College London (United Kingdom), Foundation-funded scientists are conducting research on mice with a retinal disease that resembles choroideremia.  One month after the correct form of the human choroideremia gene was introduced into the retinas of these mice, the investigators found evidence that the gene was functioning properly.  They are now working to improve the gene delivery system before launching human clinical studies.

X-linked Retinitis Pigmentosa Gene Therapy
Status: Initial Phase of Research Ongoing
Future Impact On: All Retinal Diseases

Several Foundation-funded scientific groups are developing gene therapies for treating X-linked retinitis pigmentosa.  One research group has focused on finding a suitable delivery system for the normal gene called RPGR, which is associated with the majority of cases of this disease.  Another researcher is examining the safety and effectiveness of different versions of the RPGR gene when introduced in the retinas of mice.  Such studies could set the stage for human clinical trials in the future.

By adding a layer of healthy cells directly to the retina, Foundation-funded scientists are zeroing in on promising treatments for saving and potentially restoring lost vision.  

There are two primary areas of study underway on retinal cell transplants.  First, several studies are investigating ways to “grow” or create healthy retinal cells from other types of cells so there will be an abundant source of new, healthy cells available for transplanting.  Second, other studies are focusing on methods for successfully transplanting the cells into damaged retinas to prevent further loss of vision.

Creating Retinal Cells from Skin Cells
Status: Initial Phase of Research Ongoing
Future Impact On: All Retinal Diseases

A Foundation-funded research team at the University of Wisconsin-Madison has developed an innovative process to transform skin cells into retinal cells. The full process involves converting skin cells into stem cells—essential building blocks for all types of cells.  From this point, the stem cells can be converted into retinal cells. This approach could give patients the ability to “grow” new healthy retinal cells from their own skin cells that can then be used after correcting the original genetic defect to prevent further vision loss.  Researchers are working to perfect the process so these cells can reliably be used in therapeutic applications like retinal cell transplants. Also, these retinal cells derived from persons with retinal degenerations are being used to screen drugs to find new treatments for these diseases.

Creating Retinal Cells from Stem Cells
Status: Initial Phase of Research Ongoing
Future Impact On: All Retinal Diseases

With the help of Foundation funding, researchers at the University of Washington (Seattle) are converting human embryonic stem cells into photoreceptor-like cells in the laboratory.  Photoreceptor cells are special nerve cells that are responsible for the critical first step in the process of converting light into vision. Researchers observed measurable improvement in visual function when these stem cell-derived photoreceptor cells were transplanted into the retinas of mice with Leber congenital amaurosis.  Such studies hold promise for treating people with any retinal disease.

Photoreceptor Transplants
Status: Moving Toward Clinical Trial
Future Impact On: All Retinal Diseases

An international research team funded by the Foundation has restored vision in mice with retinitis pigmentosa through the transplantation of developing photoreceptor cells.  The most significant breakthrough in this study is that the transplanted cells became full-fledged retinal cells, integrated into the host retina.  These findings suggest that a similar approach soon may be ready for evaluation in human volunteers.

Drug treatments are another promising area of Foundation-funded research.  Scientists are both developing new drugs and identifying existing drugs approved for other uses that also hold potential for preventing and potentially reversing vision loss.   

Harnessing Drugs for Retinal Diseases
Status: Moving Toward Clinical Trial
Future Impact On: All Retinal Diseases

With funding from the Foundation, the Medical University of South Carolina is screening 50,000 compounds to find those that can help keep photoreceptor cells in the retina healthy.  To date, Dr. Rohrer has identified two drugs that have shown promise at keeping the retina cells healthy. 

Researchers funded by the Foundation have developed a tiny capsule that is implanted behind the eye and releases retina-protecting molecules that slow vision loss.  During the human clinical trial, this pioneering treatment slowed progression of dry age-related macular degeneration. The device, produced by Neurotech Pharmaceuticals, Inc., is also being evaluated for the treatment of retinitis pigmentosa.  Some patients with Usher syndrome or choroideremia also are being enrolled in these studies.

Vitamins and supplements have the power to restore health to some damaged parts of the eye and are being investigated in Foundation-funded clinical trials.

Vitamin A & DHA
Status: Clinical Trial Underway
Future Impact On: Retinitis Pigmentosa

Foundation-funded researchers report that combining vitamin A palmitate dietary supplements with the omega-3 fatty acid DHA (docosahexanoic acid) appears to slow loss of vision in certain people with retinitis pigmentosa.  The combined therapy was found to be of the greatest benefit to people who had not previously taken vitamin A and the Foundation is funding follow up studies to understand why some individuals do see a response and some do not.

Through innovative research studies like these, the Foundation Fighting Blindness is closing in on real-life treatments and cures that will save and restore sight.  It is critical that we see current clinical trials through to their conclusion and advance more promising research to the clinical trial stage.  

Together, we can—and will—make blinding retinal diseases a thing of the past.