Intraocular Drugs and Innovative Software May Revolutionize Retinal Degenerative Disease Treatment
Researchers are exploring new therapeutic targets to prevent blindness as a result of retinal degenerative diseases. Image Source: Flickr User Dboybaker
A host of unexpected illnesses are popping up like weeds across the US, taking advantage of a rapidly aging population. Consider retinal degenerative diseases: they’re hardly new, but their prevalence in North America is increasing at an unprecedented rate. And from diabetic macular edema to age-related macular degeneration (AMD), there are few good treatments for degenerative diseases that attack the retina.
We do have some information about their underlying causes: diabetic macular edema appears to be correlated with the obesity epidemic, while the use of computer screens with high-frequency blue light, plus frequent exposure to ultraviolet light, has been tied to age-related macular degeneration.1 However, for both of these disorders, prevention is still the preferred method of treatment—and morbidity is often inevitable.
But change is on the horizon. In March, Regeneron and Bayer announced they would be collaborating to develop a new combination intraocular therapy to target serious eye disease. This therapy uses the angiopoietin2 (Ang2) antibody “nesvacumab” and the vascular endothelial growth factor (VEGF) trap “aflibracept” to influence the pathological development of new blood vessels and the permeability of blood vessel walls in the hope of mitigating, stopping or reversing the effects of these degenerative illnesses.2 Although this is a step in the right direction, there is still an imminent need for better medications.
Targeting Blood Vessel Creation and Maturation
Currently, there are no approved treatments for retinal degenerative diseases that will reverse vision loss. A number of therapies on the market promise to stop or slow progression, but even these are problematic. Previous intraocular therapies have required frequent injections, posing both cost and compliance problems for patients.
These treatments include Lucentis (ranibizumab), a monoclonal antibody, and Mucagen (pegaptanib), a single-stranded nucleic acid, which both act on VEGF and are injected directly into the eye. Eylea, the predecessor to the Regeneron and Bayer drug now in development, works similarly and has typically been administered to treatment-resistant patients. Promising results have been observed from these treatments, but—in addition to frequency and cost concerns—side effects can include inflammation, increased eye pressure, traumatic cataracts, and detached retinas.
Technology has advanced substantially since the initial research and development of these intraocular drugs, and as scientists continue to investigate VEGF treatment, innovative software can help them develop targeted biologic therapeutics. Additionally, it may be possible to apply many new biologic technologies, such as CRISPR, to degenerative disorders after only mild modifications.
There’s reason to think that researchers will also begin to identify new targets and move away from the single target approach, following the lead of the Regeneron/Bayer drug now in development. Therapies targeting multiple pathways simultaneously have the potential to be more potent, as there are a number of molecular failures that lead to vision loss in retinal degenerative diseases.
Looking Beyond VEGF Modification
Non-drug based therapies have always required surgery, which is often quite traumatic for an elderly patient base—although surgical options are getting better. For instance, the FDA recently approved a tiny, implantable “telescope” that improves vision by magnifying images onto the patient’s retina. While it might seem straight out of a science fiction novel, this mini-telescope has successfully been used for patients with AMD and for visually impaired patients with Stargardt’s macular dystrophy.3 The treatment is currently covered by Medicare for eligible patients in the United States; however, it is still invasive and thus not a viable choice for many people.
Laser photocoagulation is another technique aimed at treating the eye’s vasculature. This treatment destroys or seals off new blood vessels, but it also creates a plethora of retinal scars. Since retinal scarring may lead to blind spots, this particular side effect could render the therapy ultimately futile. In attempts to circumvent the risk of scarring, another laser therapy option works in conjunction with injectible medication: a low-level laser is shone into the patient’s eyes to activate Visudyne, which is injected into the patient’s arm.
Once activated, a chemical reaction occurs that obliterates abnormal blood vessels. Site-accurate activation is a technique that researchers are beginning to explore more heavily now that they have the tools to do so. With the aid of advanced lab software, researchers can more easily model and pair therapeutics and delivery systems to reverse or better prevent progression of retinal degenerative diseases.
Finding New Uses for Existing Medications
As researchers also become better able to model the molecular processes which lead to vision loss, it stands to reason that they will be able to create increasingly more complex therapeutics. For instance, by analyzing the process by which CD59 and lysosomes act to protect the retinal pigment epithelium (RPE) from complement attack, scientists have identified new therapeutic targets. CD59 prevents the formation of pores in the RPE cells, while lysosomes move in to plug the pore.4 By studying this process, researchers were able to identify an enzyme—activated by excess cholesterol in the RPE—that is responsible for neutralizing protective mechanisms.
They also realized that there are a number of existing drugs, many of them related to mental health, that mitigate this enzyme’s activity. Modern lab software allowed the researchers to perform a full epidemiological analysis, confirming that the long-term use of medications that blocked this enzyme correlated with decreased susceptibility to macular degeneration. The team then took their research a step further by providing proof of concept via a model organism. They were able to demonstrate that administering these drugs resulted in restored CD59, a reactive oxygen species decrease, and the prevention of mitochondrial fragmentation.
Sophisticated studies like this generate a lot of data and require quick and accurate analysis. BIOVIA Biologics is a suite of process experiences supported by a common platform that helps researchers rapidly analyze and organize their data. The software provides key capabilities in documentation and data management that allow investigators to better analyze enzymes and the therapeutic epidemiological pathway. It also provides real-time project tracking that can be synced between different sites. There is an urgent need for better therapeutics for retinal eye diseases; broadening the scope of the therapeutics being developed may be the key to saving sight. Please contact us today to learn more about how our software options can support the efforts of your lab.
- “The Lowdown on Blue Light: Good vs. Bad, and Its Connection to AMD,” February 2014, https://www.reviewofoptometry.com/ce/the-lowdown-on-blue-light-good-vs-bad-and-its-connection-to-amd-109744 ↩
- “Regeneron and Bayer To Jointly Develop Novel Combination Therapy for Eye Diseases,” March 24, 2016, http://www.prnewswire.com/news-releases/regeneron-and-bayer-to-jointly-develop-novel-combination-therapy-for-eye-diseases-300240765.html ↩
- “Macular Degeneration Treatment,” November 2015, http://www.allaboutvision.com/conditions/amd-treatments.htm ↩
- “Macular degeneration insight identifies promising drugs to prevent vision loss,” July 18, 2016, http://medicalxpress.com/news/2016-07-macular-degeneration-insight-drugs-vision.html ↩