Sign up for emails to stay up to date on the latest Foundation news and research. Gyroscope Therapeutics, a gene-therapy development company in the UK, has launched the first gene therapy clinical trial for the dry form of age-related macular degeneration AMD. Audio version: Gyroscope Therapeutics, a gene-therapy development company in the UK, has launched the first gene therapy clinical trial for the dry form of age-related macular degeneration AMD.
Robert MacLaren , professor of ophthalmology at the University of Oxford, and will be taking place at three locations in the UK. MacLaren, who is also the lead investigator for X-linked retinitis pigmentosa and choroideremia gene therapy clinical trials. Hence it is logical now to explore early preventative interventions that might have an impact in stopping progression of this disease.
The emerging Gyroscope treatment was developed to slow the progress of dry AMD, thereby preventing or slowing debilitating central vision loss. Therapy developers believe a single subretinal injection of the gene therapy may work for several years or the lifetime of the patient.
However, researchers have learned that the complement system is overactive in people with AMD, leading to degeneration of the macula, the central region of the retina.
AMD is the leading cause of blindness in people over 50 in developed countries. The condition affects approximately 10 million people in the US and million worldwide.
Risks for AMD include increasing age and smoking. These vessels may leak blood or other fluids, causing scarring of the macula. About 15 years ago, scientists created drugs that interfere with this process by blocking a protein called vascular endothelial growth factor VEGF. Before the creation of these so-called anti-VEGF drugs, people with wet AMD were almost certain to develop severe vision loss or blindness.
These drugs stabilize or improve vision in the vast majority of patients. But they must be injected into the eye on a regular basis. The problem is most people need an injection every four to eight weeks to keep their vision.
This can be a difficult schedule to maintain for many elderly patients struggling with other maladies and reliant on others to get them to their ophthalmology visits. Some of the most exciting research today is looking at better alternatives to frequent injections. Gene therapy is a promising alternative to ongoing eye injections of drugs such as Eyelea, Lucentis and Avastin. Despite the promise of gene therapy, the long-term effectiveness remains to be seen. Among the challenges it faces is the likely sky-high cost of such a treatment.
One promising approach that could be available soon is a refillable drug reservoir. No bigger than a grain of rice, the port is implanted into the wall of the eye, just under the eyelid, during a surgical procedure. The device continuously releases drug to the back of the eye over time. The device can be refilled using a special needle. The latest studies show many people treated this way were able to go 15 months in between treatments.
But what if one drug could treat two underlying causes of AMD? It targets both VEGF and the protein angiopoietin The latest research shows patients could go up to four months in between treatments. However, this data is so new that it has not yet been published in a peer-reviewed journal. It may also be possible to combine two drugs and hit wet AMD with a double punch. These combos could improve vision and make injections last longer. The complement part of the immune system is thought to attack the retina.
Inhibiting the complement cascade can protect the retinas of mice. While two phase II trials by Genentech targeting the complement protein called factor D in geographic atrophy patients were not successful, a phase II trial by Apellis targeting a different complement protein called C3 showed promising results.
The Apellis drug has now moved into phase III trials. Similarly, another drug called Zimura, which targets the complement protein C5, slowed the growth of geographic atrophy in a phase II trial, and has moved on to a phase II trial. Both of these drugs are injected into the vitreous jelly in the center of eye.
Another approach is to try to inhibit specific immune cells with the oral antibiotic doxycycline. This is in phase II clinical trials. In an approach to limit the toxic byproducts of vision cells, an oral drug called ALK is being tested in phase II clinical trials for GA. This drug is a modified deuterated version of vitamin A that inhibits formation of the toxic byproduct A2E.
A different approach is to limit the workload of the photoreceptors vision cells , thus limiting potentially toxic by-products of that work. A potential side effect is some degree of night blindness, or difficulty seeing in low light.
Unfortunately, a clinical trial for patients with geographic atrophy showed that this drug did not slow the growth of the atrophy. One drug that showed positive results in a phase II trial is brimonidine, which also lowers eye pressure and is used as an eye drop in glaucoma patients.
Cell transplantation is also being tested. These cells are important because the photoreceptors die without them. RPE cells can be produced from other cells, then injected under the retina.
Early clinical trials have suggested that this approach can be safe.
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