PBM CEO Paul B. Manning, a director of the National Neurovision Research Institute (NNRI), is on a mission to improve the lives of people with dry macular degeneration (Stargardt disease) and other related retinal degenerative diseases that cause substantial vision loss. He and his wife Diane are the parents of two children with Stargardt disease and have spent more than $1 million funding ambitious research projects that have now led to a promising new gene therapy.

In October 2006, the NNRI, the clinical trial support organization of the Foundation Fighting Blindness (FFB), announced an agreement with Oxford BioMedica, a biopharmaceutical company in the United Kingdom, to collaborate on the development of the StarGen™ gene therapy for the treatment of Stargardt disease and other related conditions. A primary goal of the agreement is to initiate a Phase I clinical trial of StarGen by the end of 2007.

Stargardt disease is caused by harmful mutations in a gene called ABCA4, which was discovered by a research team led by Rando Allikmets, Ph.D., the Acquavella Associate Professor in Ophthalmology, Pathology and Cell Biology at Columbia University Medical Center. As a result of the mutations, a critical protein involved in normal retinal cycle function is not produced, leading to progressive loss of vision. The StarGen treatment, as currently performed in Dr. Allikmets’ laboratory on animal models, involves adding a normal ABCA4 gene using Oxford BioMedica’s proprietary LentiVector® gene delivery system, to mice lacking functional ABCA4 (replacement of the mutant ABCA4 gene with a normal gene), thereby serving as a promising treatment for any retinal disease caused by ABCA4.

“We are very excited about this new treatment that may one day help children and adults stricken by dry macular degeneration and other diseases caused by the ABCA4 gene,” said Manning. “StarGen represents a culmination of strategic funding by the Foundation Fighting Blindness and the resulting collaboration of Oxford BioMedica and Dr. Allikmets to move a gene therapy for dry macular degeneration into human studies.”

“Generous support from Mr. and Mrs. Manning over many years has allowed us to set up a comprehensive gene therapy program for treating ABCA4-related diseases at Columbia, which now has shown very promising results in pre-clinical stage,” added Dr. Allikmets.

"We are delighted that a promising treatment for Stargardt disease and related conditions is taking a major step toward study in humans," says Bill Schmidt, Chief Executive Officer, Foundation Fighting Blindness. "StarGen gives real hope to many people throughout the world who are affected by a disease that causes substantial vision loss in adolescence and young adulthood."

About Stargardt Disease

According to the FFB, Stargardt disease (also Stargardt's Disease) is the most common form of inherited juvenile macular degeneration. It is characterized by a reduction of central vision with a preservation of peripheral (side) vision.

Clinical Description

Stargardt disease, also known as fundus flavimaculatus, is usually diagnosed in individuals under the age of 20 when decreased central vision is first noticed. On examination, the retina of an affected individual shows a macular lesion surrounded by yellow-white flecks, or spots, with irregular shapes. The retina consists of layers of light-sensing cells that line the inner back wall of the eye and are important in normal vision. The macula is found in the center of the retina and is responsible for the fine, detailed central vision used in reading and color vision.

The progression of visual loss is variable. One study of 95 individuals with Stargardt disease showed that once a visual acuity of 20/40 was reached, there was often rapid progression of additional visual loss until acuity was reduced to 20/200 (legal blindness). By age 50, approximately 50 percent of all those studied had visual acuities of 20/200 or worse. Eventually, almost all individuals with Stargardt disease are expected to have visual acuities in the range of 20/200 to 20/400. The reduced visual acuity due to Stargardt disease cannot be corrected with prescription eyeglasses or contact lenses. In late stages of the disease, there may also be noticeable impairment of color vision.

Inheritance

Stargardt disease is almost always inherited as an autosomal recessive disorder. It is inherited when both parents, called carriers, have one gene for the disease paired with one normal gene. Each of their children then has a 25 percent chance of inheriting the two copies of the Stargardt gene (one from each parent) needed to cause the disease. Carriers are unaffected because they have only one copy of the gene. At this time, and until the disease gene is identified, it is impossible to determine who is a carrier for Stargardt disease until after an affected child is diagnosed.

Treatment

In 1997, Foundation researchers isolated the gene for Stargardt disease. The ABCR gene (also known as ABC4A) produces a protein involved in energy transport to and from photoreceptor cells in the retina. Mutations in the ABCR gene, which cause Stargardt disease, produce a dysfunctional protein that cannot perform its transport function. As a result, photoreceptor cells degenerate and vision loss occurs. The discovery of the ABCR gene now allows researchers to study the underlying biochemical interactions that result from mutations in this gene. Understanding how genetic mutations lead to retinal degeneration is critical for the development of experimental therapies. Although there is currently no treatment for Stargardt disease, individuals may benefit from the use of low vision aids and training.

People affected by Stargardt disease often wear sunglasses for comfort and to try and minimize any potential vision loss from excessive light exposure.(Source: FFB)

About The Foundation Fighting Blindness

The urgent mission of The Foundation Fighting Blindness is to drive the research that will provide preventions, treatments, and cures for people affected by Stargardt disease, retinitis pigmentosa, macular degeneration, Usher syndrome, and the entire spectrum of retinal degenerative diseases. The National Neurovision Research Institute is a support organization of FFB, which was established to accelerate the translation of laboratory-based research into clinical trials for treatments and cures of retinal degenerative diseases.