Progress In Vision Research: The Year in Review
From the Foundation Fighting Blindness Newsletter

[Genetic Research]
[Gene Therapy]
[Medical Therapy]
[Retinal Cell Transplants]
[The Future]

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Over the past year, Foundation-funded scientists made remarkable progress toward finding treatments and cures for retinal degenerative disease. The Foundation's investment in research is beginning to propel experimental therapies from the laboratory to clinical trial investigation. We can now glimpse a day when doctors will recruit patients for clinical trials testing gene therapy, medical therapy and retinal cell transplantation. While we have our sights set on the future, it is heartening to recount all of the progress that occurred in 1997.

Genetic Research
In March, a collaborative research team, funded in part by The Foundation, discovered the gene which causes Stargardt disease. Stargardt disease is the most common early onset form of macular degeneration. In September, this same research team reported that mutations in this gene, known as the ABCR gene, also cause an estimated 16 percent of age-related macular degeneration cases. This stunning breakthrough provided the first concrete evidence that AMD has a major genetic component.
In October, Foundation-funded researchers found mutations in two genes that cause autosomal recessive retinitis pigmentosa. These genes, called "RPE 65" and "CRALBP", are the first RP genes to be found in the retinal pigment epithelium (RPE). The RPE is a cell layer that supports the function of photoreceptor cells in the retina. Researchers have long speculated that some forms of RP might be caused by gene mutations in RPE cells. However, almost all of the other genes found to cause RP are active in photoreceptor cells. The discovery of the RPE 65 and CRALBP genes should spur closer examination of genes that are active in RPE cells.
In November, a collaborative research group funded in part by The Foundation, isolated the first gene found to cause a severe, early onset retinal degeneration called cone-rod dystrophy. This genetic form of the disease is clinically known as CORD2 (cone-rod dystrophy 2). Individuals with cone-rod dystrophy first experience central vision loss followed by night blindness and peripheral vision loss. Previous studies of patients thought to have CORD2 found that central vision loss begins in the first decade of life with the onset of night blindness occurring sometime after age 20. Little visual function remains after the age of 50.
The Foundation is deeply committed to finding all of the genes responsible for these blinding diseases. An understanding of how a defective gene leads to vision loss is crucial in developing effective treatments and cures.

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Gene Therapy
Gene therapy holds tremendous potential for the future treatment of retinal degenerative diseases. Although much work lies ahead, researchers are developing treatments that might one day replace non-functional genes or silence harmful genetic mutations. In a major breakthrough, scientists have delayed retinal degeneration in a rodent with rapid onset retinal degeneration by delivering healthy genes to photoreceptor cells.
This breakthrough demonstrated that gene therapy can work. However, further success is dependent on refining gene delivery systems that can transport healthy genes into retinal cells. In scientific jargon, gene delivery systems are called vectors. Most vectors are genetically altered viruses. Viruses are extremely effective at infiltrating the nucleus of a cell. However, viruses also carry harmful genetic information that evoke immune responses. Immune responses jeopardize any potential therapeutic value the healthy gene might offer. Scientists are currently working to genetically alter vectors that will deliver healthy genes to retinal cells without evoking damaging immune responses.
Drs. Debora Farber and Rajendra Kumar-Singh of The Foundation's Research Center at UCLA have developed a promising new vector called an "encapsidated adenovirus minichromosome" (EAM). This new vector seems to have eliminated much of the harmful genetic elements of the virus while still retaining its gene delivery capabilities. Although further testing is necessary, this vector has shown promise in preliminary experiments in rodents.
Due to recent progress in gene therapy research, The Foundation will sponsor a gene therapy symposium in February. The symposium will allow the world's leading genetic researchers to assess current research and identify future directions. We will report on this meeting in future newsletters.

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Medical Therapy
Over the past year, The Foundation Fighting Blindness, The National Eye Institute and Regeneron Pharmaceuticals have been coordinating research efforts to advance survival factor therapies from the laboratory to human clinical trial investigation. Survival factors are substances produced by the body that sustain nerve cells. In laboratory research, a survival factor developed by Regeneron called Axokine has shown the ability to save degenerating photoreceptor cells and delay their death. Although further work is needed before Axokine can be tested in patients, The Foundation and its Scientific Advisory Board think this experimental therapy has shown enough promise in the laboratory to warrant consideration of clinical trial testing. The Foundation is hopeful that survival factors will one day preserve vision in humans.
In the coming year, Foundation researchers will be further testing the efficacy and safety of Axokine to gain FDA approval for future clinical trial testing. Partnerships with pharmaceutical and biotechnology companies, such as Regeneron, are critical in gaining access to new drugs that might arrest or slow retinal degeneration. Through its Medical Therapy Program, The Foundation is actively seeking these partnerships.

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Retinal Cell Transplantation
In addition to laboratory studies funded by The Foundation, several research groups have begun performing experimental retinal cell transplants in humans. In June, The Foundation sponsored a scientific symposium to evaluate current research. At the symposium, transplant scientists presented their most recent results.
This meeting was extremely helpful in evaluating transplant research and identifying future directions. Human transplant research did not show any clear indication of efficacy either in preventing vision loss or restoring sight. Immune rejection was identified as a common complication that must be addressed. However, laboratory research showed progress in overcoming hurdles still confronting this experimental treatment modality.
One major laboratory breakthrough concerns the supply of healthy donor cells. Although helpful for research purposes, neither embryonic nor adult cells represent an ideal source should transplantation become a viable treatment option. Clearly, an abundant supply of healthy donor cells would become critical. One possible source of tissue might be transformed cells. Transformed cells have the ability to reproduce themselves in large quantities in culture. Dr. Raymond Lund, a Foundation-funded scientist from the Institute of Ophthalmology in London, presented data demonstrating that transformed RPE cells can delay photoreceptor degeneration when transplanted into a rodent with a gene defect in its RPE cells.
Although human experiments have not yet demonstrated success, The Foundation remains optimistic that retinal cell transplantation may one day offer patients a safe and effective treatment. Clearly, laboratory research must overcome remaining obstacles to clear the way for future success in clinical trial research.

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The Future
As experimental therapies advance to the clinical trial arena, funding becomes ever more costly. To keep pace with the financial demands of vision research, The Foundation has embarked on an ambitious plan to double its funding commitment over the next five years. The Foundation is also partnering with pharmaceutical and biotechnology companies to test drugs and agents that may offer therapeutic benefit. Such relationships are attracting a greater investment in vision research. In short, The Foundation is committed to the urgent goal of finding treatments and cures for retinal degenerative disease.
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Date last modified February 9, 1998