| Stargardt disease |
| Classification and external resources |
| ICD-10 |
H35.5 |
| OMIM |
248200 600110 603786 |
| DiseasesDB |
31282 |
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. The onset of symptoms usually appears between the ages of six and thirty years old (average of about 16–18 years). Several genes are associated with the disorder. Symptoms typically develop by twenty years of age, and include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.
Contents
- 1 Signs and symptoms
- 2 Genetics
- 3 Pathophysiology
- 4 Treatment
- 5 Prognosis
- 6 Epidemiology
- 7 Research
- 8 History
- 9 References
- 10 External links
Signs and symptoms
The main symptom of Stargardt disease is loss of visual acuity, which ranges from 20/50 to 20/200.[1] Those with Stargardt disease are sensitive 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. Symptoms usually appear before age 20. Symptoms include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.[2][3]
Genetics
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.
Pathophysiology
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 a 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).
Treatment
Clinical trials are being conducted with promising results. It is said that the trials can halt and possibly even reverse the effects of Stargardt's disease using stem cell therapy [4]
Prognosis
The long-term prognosis for patients with Stargardt disease is widely variable although the majority of people will progress to legal blindness.[1]
Stargardt disease has no impact on general health and life expectancy is normal.[5] Some patients are able to drive.
Epidemiology
STGD1 is the most common form of inherited juvenile macular degeneration with a prevalence of approximately 1 in 10,000 births.[2]
Research
Treatment modalities currently under clinical investigation include cell therapy, gene therapy and oral therapies.
However, recently a technology called esight has been developed that allows users who are legally blind, including those with Stargardt's disease, to see. While the technology does not work for people who are totally or profoundly blind, anyone who still retains some vision, however slight, may benefit from it.[6] It is important to understand that this technology has yet to be tested formally and currently only anecdotal data is available.
On November 22, 2010, it was announced that Advanced Cell Technology,[7] 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.[8] 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.[9] In October 2014, the results of the Phase I/II clinical trial were published in the Lancet.[10]
Gene therapy trials are also on-going and supported by the company Oxford Biomedica. 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 sponsored by Alkeus Pharmaceuticals. ALK-001 is a 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.
ACT, Oxford Biomedica and Alkeus Pharmaceuticals have all received orphan drug designation in the United States for the treatment of Stargardt Disease.
Preclinical research include a new compound that can remove lipofuscin from retinal pigment epithelial cells.[11] The compound drug has been granted orphan drug designation for the treatment of Stargardt disease by the European Medicines Agency.
History
The disease was discovered in 1909 by Karl Stargardt, an ophthalmologist in Berlin.[12][13]
In 1997, it was discovered that mutations in the ABCA4 gene cause Stargardt. 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.[2]
References
- ^ a b Yanoff, Myron; Duker, Jay S. (2008). Ophthalmology (3rd ed.). Edinburgh: Mosby. pp. 560–562. ISBN 978-0323057516.
- ^ a b c Stargardt Disease
- ^ "Stargardt's". Lowvision.org. 1997-03-03. Retrieved 2012-12-05.
- ^ [1]
- ^ Stargardt Disease from The University of Arizona College of Medicine, Department of Ophthalmology and Vision Science. Retrieved Jan 2012
- ^ [2]
- ^ "Advanced Cell Technology Receives FDA Clearance For the First Clinical Trial Using Embryonic Stem Cells to Treat Macular Degeneration". Advanced Cell Technology.
- ^ "ACT Receives Approval from Data and Safety Monitoring Board (DSMB) to Treat Next Patients in Stem Cell Clinical Trials". Advanced Cell Technology. Retrieved 2012-12-05.
- ^ "Advanced Cell Technology Receives Approval from Data Safety Monitoring Board (DSMB) to Initiate Treatment of Third Patient Cohort in All Three Clinical Trials". Advanced Cell Technology. 2013-03-14. Retrieved 2013-03-17.
- ^ http://download.thelancet.com/flatcontentassets/pdfs/S0140673614613763.pdf
- ^ Lipofuscin can be removed from the retinal pigment epithelium of monkeys. Julien S, Schraermeyer U. Neurobiol Aging. 2012 Oct;33(10):2390-7. doi: 10.1016/j.neurobiolaging.2011.12.009. Epub 2012 Jan 12.
- ^ synd/2306 at Who Named It?
- ^ K. B. Stargardt. Über familiäre, progressive Degeneration in der Makulagegend des Auges. Albrecht von Graefes Archiv für Ophthalmologie, 1909, 71: 534-550.
External links
- Stargardt's Disease - from the American Macular Degeneration Foundation
- Stargardt's sease - from TheRetinaSource
- Stem Cell Research NPR Special Report - from NPR
|
Genetic disorder, membrane: ABC-transporter disorders
|
|
| ABCA |
- ABCA1 (Tangier disease)
- ABCA3 (Surfactant metabolism dysfunction 3)
- ABCA4 (Stargardt disease 1, Retinitis pigmentosa 19)
- ABCA12 (Harlequin-type ichthyosis, Lamellar ichthyosis 2)
|
|
| ABCB |
- ABCB4 (Progressive familial intrahepatic cholestasis 3)
- ABCB7 (ASAT)
- ABCB11 (Progressive familial intrahepatic cholestasis 2)
|
|
| ABCC |
- ABCC2 (Dubin–Johnson syndrome)
- ABCC6 (Pseudoxanthoma elasticum)
- ABCC7 (Cystic fibrosis)
- ABCC8 (HHF1, TNDM2)
- ABCC9 (Dilated cardiomyopathy 1O)
|
|
| ABCD |
- ABCD1 (Adrenoleukodystrophy, Adrenomyeloneuropathy)
|
|
| ABCG |
- ABCG5 (Sitosterolemia)
- ABCG8 (Gallbladder disease 4, Sitosterolemia)
|
|
|
see also ABC transporters
|
Index of cells
|
|
| Description |
- Structure
- Organelles
- peroxisome
- cytoskeleton
- centrosome
- epithelia
- cilia
- mitochondria
- Membranes
- Membrane transport
- ion channels
- vesicular transport
- solute carrier
- ABC transporters
- ATPase
- oxidoreduction-driven
|
|
| Disease |
- Structural
- peroxisome
- cytoskeleton
- cilia
- mitochondria
- nucleus
- scleroprotein
- Membrane
- channelopathy
- solute carrier
- ATPase
- ABC transporters
- other
- extracellular ligands
- cell surface receptors
- intracellular signalling
- Vesicular transport
- Pore-forming toxins
|
|
|
