|Classification and external resources|
|OMIM||248200 600110 603786|
Stargardt disease, or fundus flavimaculatus, is an inherited form of juvenile macular degeneration that causes progressive vision loss usually to the point of legal blindness. Several genes are associated with the disorder. Symptoms, mainly vision loss, typically develop before age 20, and also include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.
Characteristics and symptoms
The main symptom of Stargardt disease is loss of visual acuity, which ranges from 20/50 to 20/200. Other symptoms include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting. The disease causes sensitivity to glare; overcast days offer some relief. Vision is most noticeably impaired when the macula (center of retina and focus of vision) is damaged, leaving peripheral vision more intact. Generally, vision loss starts within the first 20 years of life.
Stargardt disease is associated with several different genes:
- STGD1: The most common form of Stargardt disease is the recessive form caused by mutations in the ABCA4 gene. It can also be associated with CNGB3.
- STGD3: There is also a rare dominant form of Stargardt disease caused by mutations in the ELOVL4 gene.
- STGD4: Associated with PROM1.
The classification "STGD2" is no longer used.
In STGD1, the genetic defect is manifest in the visual phototransduction cycle. The ATP-binding cassette transporter (ABCA4) is defective and leads to rapid formation of toxic vitamin A dimers (also known as bisretinoids), which then build up in fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina.
In STGD4, a butterfly pattern of dystrophy is caused by mutations in a gene that encodes a membrane bound protein that is involved in the elongation of very long chain fatty acids (ELOVL4).
Clinical trials are being conducted with promising early results. The trials may one day lead to treatments that might halt, and possibly even reverse, the effects of Stargardt disease using stem cell therapy.
The long-term prognosis for patients with Stargardt disease is widely variable although the majority of people will progress to legal blindness.
STGD1 is the most common form of inherited juvenile macular degeneration with a prevalence of approximately 1 in 10,000 births.
Treatment modalities currently under clinical investigation include cell therapy, gene therapy and oral therapies. Anecdotal evidence suggests that new technology called esight may help some individuals with Stargardt who retain some visual function, recover vision.
On November 22, 2010, it was announced that Advanced Cell Technology, now called Ocata Therapeutics, received United States Food and Drug Administration clearance to immediately initiate a Phase I/II multicenter clinical trial using retinal cells derived from human embryonic stem cells (hESCs) to treat patients with Stargardt’s Macular Dystrophy. In September 2011, ACT announced they were beginning the next stage of treatment for SMD, and Dry AMD as the first stage proved to be safe by an independent board of experts. In March 2013, after treating and collecting data on 18 patients, Advanced Cell was given approval to test its stem cell therapy on patients with 20/100 vision. In October 2014, the results of the Phase I/II clinical trial were published in the Lancet.
Gene therapy trials are also on-going. During gene therapy, a working copy of the ABCA4 gene is incorporated in a lentivirus (an inactivated virus which transports the working copy of the gene) and injected into the eye through a subretinal injection. It is hoped that such injection, if performed early enough, could prevent the progression of the disease.
Finally, oral therapies that are being investigated include ALK-001, modified vitamin A delivered orally which prevents the formation of toxic vitamin A dimers in the eye. ALK-001 has completed a phase 1 clinical trials.
Preclinical research include a new compound that can remove lipofuscin from retinal pigment epithelial cells. The compound drug has been granted orphan drug designation for the treatment of Stargardt disease by the European Medicines Agency.
In 1997, it was discovered that mutations in the ABCA4 gene cause Stargardt disease. The mutations cause the production of a dysfunctional protein that cannot perform energy transport to and from photoreceptor cells in the retina. The photoreceptor cells then degenerate, causing vision loss.
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