Stargardt disease is an inherited form of macular degeneration caused by genetic mutations which alter proteins that block nutrients and waste from reaching cells located at the central portion of retina known as the macula. Treatment aims at minimizing loss of vision through sealing leaky blood vessels in retina, and using low vision aids like magnifiers and telescopes.

Gene Therapy

Gene therapy treatments work by replacing or supplementing genetic mutations responsible for diseases with healthy versions, with researchers developing many such treatments currently in clinical trials – many using genetically modified viruses to deliver replacement genes to retinal pigmented epithelial (RPE) cells of the eye.

RPE cells play an essential role in maintaining normal vision. You’ll find these RPE cells near the optic nerve at the back of the eye; by targeting these RPE cells with stargardt gene therapy or another form of macular degeneration therapy, patients could experience restored vision.

A number of companies have recently raised large sums to advance their gene therapy technologies, including AAVantgarde Bio SrL which raised EUR61 million for its series A round to develop an approach that exceeds packaging limitations in adeno-associated virus vectors and allow these viruses to carry much longer genes than they currently can. They hope to launch their first program clinically later this year.

Another approach to gene therapy, known as cloning, can also help. Couples who know they carry the recessive gene for stargardt disease could utilize in vitro fertilization and screen their embryos during IVF for abnormalities related to stargardt. Any embryo with abnormal genes would be discarded while an embryo with normal genes could have their nucleus transferred into an egg to produce a cloned embryo with its regular genes which would then be implanted back into their mother’s womb where it would develop normally as an adult.

As with other gene therapies, gene therapy for stargardt can be prohibitively expensive even if it does manage to cure the disease. Thankfully, other retinal treatments are becoming more affordable; for instance, an oral treatment to increase mitochondrial function has recently entered clinical trials for dry age-related macular degeneration – potentially making this approach useful in treating Stargardt’s.

Other treatments may also help preserve existing retinal pigmented epithelial cells. An experimental drug called multi-characteristic opsin, or MCO, has been developed by Nanoscope Therapeutics of Dallas Texas as an MCO therapy in order to sensitize RPE cells to detect light and improve vision in macular degeneration patients by stimulating them into responding appropriately. As well as being evaluated as potential treatment for Stargardt’s disease and retinal degenerations.

Retinal Pigment Epithelial Cells

Retinal pigment epithelial (RPE) cells form an essential layer in the retina, lying between photoreceptors and Bruch membrane/choriocapillaris. They serve a number of essential functions, including phagocytosis of shed photoreceptor outer segment membrane, transport of nutrients and metabolites, vitamin A metabolism and maintenance of an effective immune privilege system – degeneration of these RPE cells being at the core of Stargardt Disease as well as numerous hereditary macular degenerations.

Scientists are exploring methods to restore the function of RPE by replacing it with healthy cells. RPE cells provide essential support functions to retina’s photoreceptors, so by reinstating their function scientists hope to slow or even stop stargardt eye disease from progressing further.

Echothiophate iodide, a topical compound commonly used to treat glaucoma and strabismus, has long been tested in humans as one of the treatments. By inhibiting acetylcholinesterase enzyme that breaks down neurotransmitters in retina, this medication reduces waste build-up under retina, improving visual acuity.

Human embryonic stem cell injection may provide another promising solution, replacing damaged RPE cells and possibly restoring visual processing abilities. While still experimental, this therapy could prove more successful at treating Stargardt disease than traditional methods.

Alongside experimental therapies, researchers are also exploring alternative ways of improving macula function. One case study demonstrated how Stargardt patients taking low doses of echothiophate iodide experienced improved visual acuity and color vision.

Stargardt’s disease sufferers can benefit from many of the same tools available to those dealing with age-related macular degeneration, including magnifiers and screen magnifying software. A physician may also order an Amsler grid or fluorescein angiography scan in order to evaluate and monitor retinal blood vessel health while tracking disease progression.

Subretinal Injections

Stargardt eye disease is caused by a genetic mutation that alters protein to prevent retinal cells from receiving essential nutrients and waste products from retinal cells. As these waste byproducts accumulate beneath the retina, toxic buildup occurs which kills photoreceptors. Current treatments involve replacing dead photoreceptors with healthy ones which should work normally to restore vision clarity.

Subretinal injections could be the most promising approach. This procedure involves injecting therapeutic agents directly into the space surrounding the retina to bypass damaged areas and reach photoreceptors more directly. It has been successfully used to deliver viral vectors, pharmacological agents and stem cells directly into mice retinal pigment epithelia. Furthermore, subretinal injections offer potential solutions that could have direct impacts on photoreceptors directly.

This technique enables the administration of various therapeutic genes and drugs into the subretinal space using AAV2 vectors containing cDNA for human retinal pigment epithelium 65kDa protein (RPE65). RPE65 gene plays a key role in transporting lipofuscin away from photoreceptors; results have shown promise; however further research needs to be completed on its effectiveness in patients suffering from stargardt eye disease.

Another promising treatment involves administering an injectable virus designed to repair the ABCA4 gene in those suffering from Stargardt disease. This gene provides instructions for producing the ATP-binding transporter A4 proteins necessary to remove lipofuscin from photoreceptor cells; without them, lipofuscin accumulates and kills photoreceptor cells, leading to vision loss. A Phase 1/2 half-dose escalation trial of Luxturna’s adeno-associated virus serotype 2 (AAV2)-based Luxturna was successfully completed with promising results – see Luxturna trial results here

Other treatments include extracting and transplanting retinal pigment epithelial cells that serve essential supportive roles for photoreceptors in the retina. This approach mirrors an experimental therapy for Leber congenital amaurosis due to GUCY2D mutations which has shown great promise in improving central and color vision. Other trials have explored using cholinergic medications like echothiophate iodide and pilocarpine to protect photoreceptors against breaking down prematurely.

Laser Therapy

Stargardt disease treatment currently available only slows further vision loss and helps some patients to read and drive, with some benefit to color vision as well. Unfortunately, however, it cannot restore central vision or stop its progression to legal blindness; research may identify a solution in near future.

Laser therapy involves shining a laser light directly into the eye to promote healing of injured tissues. This treatment method is performed in the doctor’s office and does not involve surgery or injections of drugs, nor heat or discomfort from exposure to light from this source. Instead, laser light stimulates your body’s natural healing processes without harming normal tissues in any way; some laser therapy techniques utilize hand-held devices while others mount onto arms or the patient’s head for maximum effectiveness.

Genetic mutations cause proteins to block the passage of nutrients and waste between photoreceptor cells of the macula and their nutrition source, leading to Stargardt disease. The condition results in blurry vision in straight lines, difficulty with recognising faces or objects, and decreased color vision.

Scientists have successfully isolated the gene that causes Stargardt disease, and preliminary research suggests that replacing it with a healthy copy could potentially slow or stop vision loss. Unfortunately, these experiments remain experimental and will take years to conclude.

Some patients suffering from Stargardt disease may require laser treatment to seal leaking blood vessels in their retina, similar to what’s done for wet age-related macular degeneration. While it can reduce vision loss caused by these leakage sites, it does not restore vision nor stop progression of disease progression.

Other treatments are being developed that can repair damage caused by mutations of the ABCA4 gene. They could involve extracting and replacing dead retinal pigmented epithelial (RPE) cells – essential support cells for photoreceptors – with healthy ones to restore vision. Research indicates this approach might even save sight.

Another strategy involves increasing mitochondrial function to speed energy production faster, which has been tested successfully in several clinical trials for dry age-related macular degeneration and has shown promise in slowing Stargardt’s disease.