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Statement in Support of Increased Funding for The National Eye Institute and Retinal Degenerative Disease Research

From the Foundation Fighting Blindness newsletter, May 1999

Editor's note: On April 13, 1999, Mrs. Betti Lidsky, a mother of three children with retinal degeneration, testified before the United States Congress on behalf of The Foundation Fighting Blindness in support of increased federal funding for The National Eye Institute. In addition to Mrs. Lidsky's testimony, The Foundation Fighting Blindness submitted a statement for the Congressional Record describing opportunities that exist to develop treatments and cures for retinal degenerative diseases. This document, reprinted below, was entered into the Congressional Record on April 13, 1999.

Established in 1971, The Foundation Fighting Blindness is a nonprofit medical research organization with an urgent mission to find treatments and cures for blinding retinal degenerative diseases like retinitis pigmentosa, macular degeneration and Usher syndrome. The Foundation is the largest private supporter of retinal degenerative disease research in the United States.

The National Eye Institute (NEI) was founded in 1968 to find treatments and cures for blinding eye diseases including retinal degenerative diseases. Together, The Foundation and The NEI represent the only significant sources of funding for retinal degenerative diseases.

Retinal degenerative diseases are stealing the vision of more than six million Americans of all ages and ethniticies. Another nine million Americans have pre-symptomatic signs of retinal degeneration. The incidence of retinal degeneration is poised to skyrocket as the babyboomer generation ages.

Retinal degenerative diseases are genetically inherited conditions commonly linked by the death of photoreceptor cells, the light sensitive cells in the retina. Photoreceptor cells absorb light, turn it into an electrical signal, and then pass the signal to the brain via the optic nerve. Retinal degenerative diseases result from genetic mutations that interfere with the function of photoreceptor cells, causing them to degenerate and die. Patients with retinal degenerative diseases experience progressive vision loss leading to legal and complete blindness. Research efforts to advance treatments and cures for retinal degenerative diseases are closely focused on developing therapies that can ameliorate this genetic dysfunction or correct disease causing genetic mutations.

When the NEI and The Foundation were first established, little if any available funding existed for these diseases. Moreover, funding for the NEI has historically lagged far behind the rest of the National Institutes of Health. Despite this funding handicap, researchers have made great progress in understanding these diseases. Research has now turned a corner; several treatments could be headed toward clinical trials in the very near future. Opportunities abound. However, there is a critical need for increased funding for the NEI to make these sightsaving treatments a reality. With increased support of the NEI, scientists can accelerate the pace of research and bring these promising treatments to the clinic. Without increased support, these treatments may very well never reach the clinic.

Below is an overview of existing opportunities that with additional NEI funding could advance treatments and cures for patients with blinding retinal degenerative diseases.

Gene Therapy

Gene therapy is the introduction of a gene or genetic information into cells for the purpose of achieving a therapeutic effect. Gene therapy can take different approaches based on the form of the disease. For example, in autosomal recessive forms of retinal degenerative disease, both copies of the gene contain mutations. In recessive and some X-linked forms of retinal degeneration, the disease causing gene mutations often produce nonfunctional proteins. Lacking the protein, the retinal cells cannot function properly. In these cases, gene replacement therapy aims to deliver a healthy functioning gene directly to the affected cells so that the cell can function properly.

In laboratory experiments, gene replacement therapy has already halted vision loss in animal models. In a recent Time magazine article, Dr. James Wilson, a gene therapy expert from the University of Pennsylvania, stated that phase 1 clinical trials of gene therapy for retinitis pigmentosa could begin in the next couple of years. Unfortunately, available funding trails far behind the potential that gene replacement therapy holds.

Gene Inactivation Therapy

In autosomal dominant forms of retinal degeneration, patients have a healthy copy of a functioning gene and a gene with a disease causing mutation. Most dominant gene mutations produce a toxic or harmful protein that damages the retinal cell. In these cases, researchers are using gene inactivation therapy to silence the destructive gene and allow the healthy gene to produce the required protein. To date the most effective form of gene inactivate therapy is known as ribozyme therapy.

Ribozyme Gene Therapy

In the August 1998 issue of Nature Medicine, scientists reported on an exciting breakthrough with ribozyme therapy for autosomal dominant forms of retinal degeneration. The research team, led Drs. William Hauswirth and Alfred Lewin, gene therapy scientists from the University of Florida, found that ribozyme therapy dramatically reduced vision loss in an animal model with dominant RP. Photoreceptor cell function was as much as 93 percent greater in the ribozymetreated eyes than in the untreated control eyes.

These stunning results demand additional funding. Researchers need support to the safety and efficacy of ribozyme gene therapy in larger animal models. If successful, FDA approval to test ribozyme therapy in humans would soon follow.


Before gene therapy can be tested in humans, the safety of gene delivery systems must be further tested. In scientific parlance, gene delivery systems are called vectors. Vectors act like a fleet of microscopic delivery trucks transporting genes into retinal cells. Most vectors are derived from viruses. Viruses are extremely effective at infiltrating the nucleus of a cell where genes reside. However viruses also contain harmful elements evoke immune responses. Over the past decade researchers have been working to genetically modify viruses to reduce, and hopefully eliminate, their harmful qualities without compromising their delivery capabilities. In addition to concern for immune response, vectors must also be designed to target only the genetically affected cell type. Without careful targeting, the gene or gene product could adversely affect the function of other healthy cell types in the body. Lastly, vectors must also regulate the expression of the gene. If the healthy gene is either overactive or inactive, retinal cells will still degenerate.

In short, further progress in gene therapy for all genetic diseases hinges on the development of safer and more effective vectors. From preliminary work with rodents, two improved vectors known as lentiviral vectors and adenoassociated vectors, seem to confer longterm expression of the gene. A third vector system, encapsidated adenovirus minichromosome (EAM), appears to have eliminated much of the harmful genetic information while still retaining its gene delivery capabilities.

In summation, there is a critical need for additional research funding to complete the safety and efficacy studies of these vectors to advance gene therapy to clinical trials in a timely fashion.

Gene Identification and Genotyping

Gene therapy is not possible without first finding the mutant genes that cause retinal degenerative diseases. Over the last decade, researchers have identified many of these genes. The NEI must continue this genetic hunt for all the genes that cause retinal degeneration. There is also a critical need to screen patients to identify the gene and mutation involved in their disease. The process of identifying patients by gene defect is called genotyping. Through genotyping, researchers can identify candidates for clinical trials to test gene therapy and other treatments. Genotyping patients with retinal degenerative diseases will require extensive resources.

Pharmaceutical Agents

Over the last decade, The NEI and The Foundation have supported research in the use of survival factors as an experimental treatment for retinal degenerative diseases. Survival factors are substances produced by the body that sustain nerve cells. In laboratory studies, certain survival factors slow the death of degenerating photoreceptor cells and preserve vision. Experiments with a variety of survival factors found that ciliary neurotrophic factor (CNTF) delays retinal degeneration in animal models. NEI and Foundation supported researchers are now working to complete the necessary preclinical studies to advance CNTF, also known as Axokine, to gain Food and Drug Administration approval for clinical trials.

Axokine is the first of several drugs showing promise in the treatment of retinal degenerative diseases. There are many new drugs that hold promise in the treatment of retinal degeneration. The NEI and The Foundation currently support efforts to test pharmaceutical agents. Unfortunately, funding resources to test these new drugs are extremely limited.

Drug Delivery

One obstacle to human testing is drug delivery. While survival factors show promise, it is not yet clear how these agents will be delivered to the retina. The retina is protected from the blood supply, making it difficult for most drugs to reach photoreceptor cells. Therefore, these factors cannot be delivered systemically via a pill or an intravenous injection.

Pharmacologists have developed ocular implants that time release antiviral drugs for the treatment of an AIDS related complication called CMV retinitis. However, in their present form, these implants are not thought to be viable for delivery of survival factors like CNTF/Axokine. For the time being, injection into the eye is the most effective method to deliver survival factors. Researchers are now working to develop slow release delivery systems that would avoid the need for frequent injections. Increased NEI funding will greatly aid the development of safe and effective drug delivery systems.

Retinal Cell Transplantation

The NEI and The Foundation first supported retinal transplantation in the 1980s when this experimental therapy was just an idea on paper. Since that time, two distinct transplant procedures have emerged. Retinal cell rescue transplants aim to halt or slow the progress of the disease by transplanting healthy retinal pigment epithelial (RPE) cells, which support the function of photoreceptors (rod and cone cells) in the retina. Replacement transplants aim to restore lost vision by transplanting healthy photoreceptor cells.

In NEI and Foundation supported laboratory studies, researchers found that retinal cell rescue transplants delay retinal degeneration in an animal model. These important studies demonstrated the first evidence of "proof of principle" that retinal cell rescue transplants can delay vision loss. This finding offers hope that such an approach can be developed as a sight-saving treatment.

More recently, vision researchers tested safety of retinal cell rescue transplants in humans. Unfortunately, symptoms consistent with immune rejection have be widely observed. These results make clear that immune rejection is a complication that must be addressed.

While immunosuppressive drugs can be administered, their longterm use leaves patients susceptible to a host of side effects and complications. Once all the immunologic elements that cause rejection are identified, optimal techniques to overcome immune complications such the use of tissue matching to insure immune compatibility or genetic modification to promote immunologic tolerance can be developed. Additional funding is needed to quickly overcome this complication so that the efficacy of retinal cell rescue transplants can be evaluated.

Photoreceptor Cell Transplants

Photoreceptor cell transplants have the potential to restore lost vision to millions Americans. Recent human experiments demonstrate that this transplant procedure is safe and does not evoke immune responses. However, there is not yet evidence that photoreceptor cell transplants can restore lost vision. There is an acute need to increase research efforts to establish "proof of principle" for photoreceptor cell transplants so this sight-restoring treatment can advance to clinical trials.

Never before have so many opportunities existed to advance promising treatments for retinal degenerative diseases to clinical trials. With increased funding to the National Eye Institute for retinal degenerative disease research, sightsaving treatments would soon become available to the millions Americans who each day lose more vision.

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Date last modified June 13, 1999