Age-related macular degeneration (AMD) affects 11 million people in the U.S. It occurs when aging causes damage to the macula, the part of the eye that controls straight-ahead vision. There are two types: dry AMD and wet AMD. Dry AMD is when the macula gets thinner with age, while wet AMD occurs when abnormal blood vessels grow in the back of the eye and damage the macula. Treatments for AMD include anti-VEGF drugs, which are injected into the eye to stop the growth of abnormal blood vessels and photodynamic therapy (PDT), a combination of injections and laser treatment. These treatments aren’t cures and, in the case of anti-VEGF treatments, their effectiveness diminishes over time. This highlights the importance of developing other treatments for the disease.
If you’ve been reading this blog for a while, you’ll know that scientists are hard at work learning more about AMD and developing alternative treatments. Three projects, one at the University of Minnesota, another at the University of Colorado, and a third at Ohio State University are working on treatments for AMD.
A research team lead by John Hulleman, PhD, associate professor and Larson Endowed Chair for Macular Degeneration Research at the University of Minnesota Medical School, identified small molecules that reduces the production of proteins linked to AMD. The researchers used unbiased drug screening, a method of testing potential treatment candidates without preconceived ideas about their effectiveness. They targeted a cellular pathway known as GSK3 and discovered that the molecules could prevent AMD in preclinical models. This shows that blocking GSK3 alters specific proteins linked to AMD, preventing the disease from developing.
“In the big picture, these results provide hope that AMD may indeed be preventable, or at least modifiable by administration of a single drug,” said Hulleman.
Currently, the standard treatment for wet AMD are anti-VEGF drugs. The problem with anti-VEGF drugs, aside from their decreasing effectiveness over time, is their high cost. The University of Colorado School of Medicine did study of biosimilars, which are nearly identical versions of biologic anti-VEGF drugs.
The research, completed in partnership with Showa University in Japan, consisted of nine randomized control trials with almost 4,000 subjects that looked at anti-VEGF treatments and biosimilars. These studies demonstrated no difference in safety or effectiveness compared to the anti-VEGF drugs currently in use.
One advantage of biosimilar drugs is that they are less expensive than the original anti-VEGF drugs, saving money for both pharmaceutical companies and consumers. This could lead to wider use of biosimilars, providing researchers with more data on their effectiveness and furthering understanding of how they work.
Many treatments for diseases utilize a specific target to help the therapy work effectively. A study at Ohio State University College of Medicine found an alternative treatment option for wet AMD. Scientists in the lab of Nagaraj Kerur, DVM, PhD wanted to investigate whether the activity of the enzyme telomerase could lead to the production of VEGF in the eye.
The lab conducted experiments on mice to confirm that telomerase plays a role in the development of wet AMD. They discovered that, compared to the control group, the expression and activity of two genes that code for telomerase were higher in mice where new blood vessel growth was induced with a laser. Additionally, the response of abnormal blood vessels to laser injury was lower in mice lacking the telomerase genes. This shows that telomerase plays an important role in disease development.
Next, they tested the effects of an experimental drug that inhibited telomerase activity. It lowered the telomerase activity in healthy mice and when injected into the eyes of mice with wet AMD symptoms, it reduced the formation of abnormal blood vessels.
While the experimental drug was effective at limiting the growth of abnormal blood vessels in mice, researchers made an interesting discovery when they tested both drugs at lower doses. A low dose of either drug had minimal therapeutic effect, but combining the two at lower doses produced the best results. While telomerase inhibition can be done independently, these drugs may be used in combination therapy to treat wet AMD.
The combined efforts from the University of Minnesota, the University of Colorado, and Ohio State University illustrate the range of approaches being explored to combat AMD. Whether it’s discovering molecules to block AMD-related proteins, validating the safety of biosimilar drugs, or using telomerase inhibitors to halt disease progression, these breakthroughs are moving the field closer to more personalized and targeted therapies. While each approach is still in development, the progress made by these teams provides hope for more effective, affordable, and accessible treatments for those suffering from both dry and wet AMD.
https://news.osu.edu/a-new-target-for-treatment-of-one-type-of-macular-degeneration/