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On April 6, 2007, the Foundation Fighting Blindness convened 17 of the world’s top Stargardt disease researchers to accelerate the advancement of emerging treatments into clinical trials.
The meeting focused on two promising Stargardt disease treatments: gene therapy and the drug fenretinide. The experts discussed how these treatments slowed or prevented vision loss, and potential strategies for moving them into and through the clinical trial process.
The meeting also included presentations on lifestyle practices to preserve vision.
A potential cure through gene therapy
FFB and the biopharmaceutical company Oxford BioMedica are collaborating on the development of StarGen™ gene therapy for the treatment of Stargardt disease. Oxford BioMedica is planning to launch a Phase I human study of the therapy in about one year.
StarGen works by delivering a normal ABCA4 gene to the retina. Most people with the recessive form of Stargardt disease have variations in the ABCA4 that lead to the build-up of lipofuscin in their retina. Lipofuscin is comprised of fats, metals, organic molecules, as well as a toxic component known as A2E. Experts believe that the accumulation of A2E is the major cause of photoreceptor death and vision loss in Stargardt disease.
Because StarGen therapy involves delivery of a normal ABCA4 gene, it may also be effective in treating people affected by other retinal diseases caused by ABCA4 variations including those individuals with certain forms of cone-rod dystrophy and retinitis pigmentosa.
In preclinical studies funded by FFB, Rando Allikmets, Ph.D., Columbia University, demonstrated that the ABCA4 gene therapy was safe and effective. Allikmets and his colleagues used a therapeutic, man-made virus to deliver the gene to the retina. He noted that the viral delivery mechanism has also shown to be effective in large animal models.
StarGen therapy may prove to be most beneficial when delivered early on in the course of disease, before substantial vision is lost. Furthermore, the treatment may effectively act as a cure, if the therapeutic gene in humans can provide the same long-term gene expression as the normal ABCA4 gene.
Fenretinide may preserve a considerable amount of vision
The biopharmaceutical company Sirion Therapeutics is currently evaluating fenretinide in a Phase II clinical trial for the treatment of dry age-related macular degeneration (AMD).
In FFB-funded preclinical studies, the drug has also shown excellent potential for slowing vision loss from Stargardt disease.
Fenretinide appears to work by slowing the accumulation of lipofuscin in the retina. Lipofuscin is a hallmark of both dry AMD and Stargardt disease.
Nathan Mata, Ph.D., Vice President, Discovery Research at Sirion, investigated fenretinide in a mouse model of Stargardt disease. He demonstrated that the drug minimized the accumulation of lipofuscin, and the toxic component A2E, by reducing the uptake of vitamin A in the retina.
Sirion has been able to move directly into a Phase II clinical study of fenretinide for dry AMD, because the drug has beenevaluated previously as a cancer treatment in earlier human studies. And, it was in those clinical trials that investigators determined that fenretinide was reducing the uptake of vitamin A.
Mata noted that Sirion chose to study fenretinide in dry AMD first, before Stargardt disease, because dry AMD’s greater prevalence would lead to a more efficient and effective clinical trial process, and ultimately, the shortest path to FDA approval.
Lifestyle measures to protect vision
Animal studies suggest that light exposure may accelerate vision loss in Stargardt disease and other retinal conditions. The experts agreed that wearing sunglasses in bright light or sunshine may help protect vision in people affected by Stargardt disease. Janet Sparrow, Ph.D., Columbia University, has demonstrated in animal studies that light triggers the production of toxic materials in the retina, which may lead to, or exacerbate, vision loss in Stargardt disease and age-related macular degeneration.
Though vitamin A is prescribed as a treatment for retinitis pigmentosa, the investigators agreed that avoidance of vitamin A supplementation is recommended for people with Stargardt disease. Dean Bok, Ph.D., University of California, Los Angeles, noted that animal studies have shown that reductions in serum vitamin A result in the reduction of A2E — a toxic component causing vision loss in Stargardt disease.
Clinical trial designs
A key goal of the April 6 meeting was to discuss clinical trial design for potential treatments. The investigators presented their research findings and disease knowledge to provide guidance for the trial design process. Key points of the discussion included: appropriate age and disease stages of trial participants; optimal measures of efficacy; and trial duration.
FFB will report on Stargardt disease clinical trial developments as they occur.
DISCLAIMER: Physicians differ in their approach to incorporating research results into their clinical practice. You should always consult with and be guided by your Physician’s advice when considering treatment based on research results.
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