ABCA4 is a genetic code that tells your body to produce a protein (lipofuscin) which blocks the normal transportation of food and waste to the retina’s delicate photoreceptor cells. which tells the body to produce a protein which blocks normal transportation of food and waste to the retina’s photoreceptor cells. Flecks of lipofuscin, or these waste deposits, build up in the retinal pigment epithelium (RPE), which is the nutritional support layer for the rods and cones of the retina. The RPE and the rods and cones break down in the presence of these waste deposits.
A rarer disease called autosomal dominant Stargardt-like macular dystrophy, similar to Stargardt, is caused by the gene ELOVL4.
While there is no cure for Stargardt disease yet, the hope of genetic therapy is real. Also if new blood vessels form under the macula because of Stargardt’s disease, this can be treated with Anti-VEGF intraocular injections like is currently treated for age related macular degeneration.
Currently, to prevent further macular degeneration from Stargardts, the following is recommended:
1. Always wear sunglasses (especially sunglasses which block UV A and B and blue light) & hat
2. Never smoke or be around smokers.
3. Avoid high dose Vitamin A: which is different from patients with Retinitis Pigmentosa. In patients with Stargardt’s, Vitamin A can actually be toxic to the eyes because the vitamin is not metabolized by cells in the eye.
So what are the next steps to be in line to get treated from a blinding disease.
1. Be in the best shape you can possibly be in: avoid getting diabetes as patients who have diabetes will not be in the first round of trials or treatment most likely as companies who are investing millions want to try these therapies on those who have the best chance of improvement.
2. Exercise, eat a low carb, gluten free diet. Avoid sugar. Avoid sodas.
3. Wear sunglasses and a hat.
4. Avoid smokers & smoking.
5. If you have Retinitis Pigmentosa, look into high dose Vitamin A Palmitate. If you have Stargardt’s disease, avoid high dose Vitamin A.
6. Find out which genetic mutation you have.
a. Either ask you MD or find a genetic counselor
b. Contact a genetic testing company to see if they test for common eye disease mutations & see how much it costs.
Genes that can have a Mutation which is associated with Eye Diseases:
1. Retinitis Pigmentosa:
b. RP1, RP2, RPGR, PRPH2, IMPDH1, PRPF31, CRB1, PRPF8, TULP1, CA4, HPRPF3, ABCA4, EYS, CERKL, FSCN2, TOPORS, SNRNP200, PRCD, NR2E3, MERTK, USH2A, PROM1, KLHL7, CNGB1, TTC8, ARL6, DHDDS, BEST1, LRAT, SPARA7, CRX
2. Stargardt disease:
3. Glaucoma: This is more complex: Reference: https://www.glaucoma.org/glaucoma/the-genetics-of-glaucoma-what-is-new.php
Primary open-angle glaucoma (POAG) is the most common type of glaucoma and has no obvious abnormality in the eye that points to a cause. Although mutations in several genes, including myocilin, optineurin, and CYP1B1, have been reported to cause POAG, these genes account for less than 10% of cases worldwide. In the past 2 years, large scale genetic studies that have examined the blood samples of thousands of glaucoma patients have been instrumental in the discovery of more common genetic risk factors for POAG. A risk factor is something that doesn’t always lead to a condition but increases the risk of having that condition. For glaucoma, these genetic factors include changes in the DNA sequences (near or in the genes such as caveolin 1 and 2 (CAV1/CAV2), CDKN2B antisense RNA, TMCO1, SIX1/SIX6, and LRP12/ZFPM2 genes) or actual loss of DNA (TBK1 and GALC), and several different genes have been implicated. How these genes cause or influence the likelihood of developing POAG is of major interest.
Glaucoma is often thought of as a disease of middle age or older adults. However there are many inherited forms of glaucoma that affect young children. Primary congenital glaucoma (PCG) is the most common childhood glaucoma affecting children from birth to age 3 and is a major cause of blindness in this young population. Mutations in the CYP1B1 gene have been found to cause PCG in children worldwide and are the dominant genetic cause for glaucoma in children in the Middle East and central Europe. In the United States only 15% of children with PCG have a mutation in CYP1B1, so there are ongoing efforts to identify additional causes in these young patients. Other types of glaucoma related to maldevelopment of the eye occur in older children – the genes implicated in these forms of glaucoma play a key role in the development of the eye, so when they malfunction they cause abnormalities in the eye’s fluid drainage system which leads to elevated eye pressures and glaucoma. The genes currently known to be associated with these forms of glaucoma include PITX2, PITX3, FOXC1, FOXE3, PAX6, LMX1B, and MAF.
Primary angle-closure glaucoma (PACG) is the second most common form of glaucoma and affects over 16 million people globally. In this form of glaucoma the drainage angle closes over time, blocking the pathway to the drainage system and causing high eye pressures. Very recently a large scale genetics study identified genetic variants that are associated with this form of glaucoma. These variants are in or near PLEKHA7, PCMTD1/ST18, and COL11A1. How these genes contribute to this form of glaucoma is not clear.
Exfoliation glaucoma (XFG), also called pseudoexfoliation glaucoma, affects millions and is the most common identifiable form of open-angle glaucoma in the world. XFG results from exfoliation syndrome, a common condition characterized by the deposit of white protein-like material that forms on the lens and within the fluid drainage system of the eye, as well as tissues throughout the body. Genetic variants of LOXL1 and CNTNAP2 genes have been associated with XFG.Researchers are currently working on how these genes contribute to the formation of these protein deposits and how these cause glaucoma.
Stargardt Disease Support Groups
Contact: Florencia Braga Menendez
Mariano Moreno 465
Buenos Aires, Argentina
Stargardt Disease: Hope for a Cure
With the passing of the Orphan Drug Act in 1983, the FDA established the Office of Orphan Product Development (OOPD), which gives incentives to biotech companies to develop promising products for the diagnosis, treatment, and cure of rare diseases. Orphan Drug Status provides tax reductions and the exclusive rights to the cure for a specific condition for a period of seven years post-approval. It encourages companies to enter a market where high costs of drug development are less likely to be recouped quickly, due to the smaller pool of individuals needing the cure.
By definition, an orphan drug is one for a disease which affects less than 200,000 Americans, or less than 5 per 10,000 people in a community. During approval of an orphan drug, the FDA recognizes that Phase III clinical trials on 1000 people might not always be possible, due to a lack of individuals with the condition in question. It provides incentive to continue the research, even when a drug doesn’t prove to be the miracle cure it was initially thought.
The OOPD administers the Orphan Products Grants Program which provides funding for clinical research in rare diseases. For example, in 2014, the biotech company Makindus received orphan designation for its lead product, MI-100, from OOPD for the treatment of Stargardt disease, a hopeful sign that progress may be made toward a cure for this debilitating juvenile illness.