Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, and current treatments do not work well enough for many patients, especially in the earlier stages of the disease. A new National Institutes of Health (NIH) grant will support promising research at University of Rochester Medicine to develop a more precise treatment approach that could help slow or prevent the damage that leads to blindness.
A Disease with Few Good Options
AMD affects the macula, the small but critical part of the retina responsible for sharp central vision used for reading, driving, and recognizing faces. The disease can develop in two major forms: dry AMD, which can lead to geographic atrophy, and wet AMD, which causes abnormal blood vessel growth. Although there are FDA-approved treatments for advanced disease, they have limited benefit, cause side effects, and do not address all stages of AMD.
“There is still a major unmet need for treatments that work earlier in the disease process and do more than simply slow down later damage,” said Ruchira Singh, PhD, with the Flaum Eye Institute and principal investigator of the project.
A New Target for Treatment
Singh’s lab is studying a protein called secretory phospholipase A2 -11A (sPLA2-IIA), which her team identified as a possible driver of AMD and related macular dystrophies. Using patient-derived stem cell models, the researchers found that elevated levels of this protein are linked to the harmful changes seen in the retina, including drusen, the early deposits that are the central hallmark of the disease.
“By studying patient cells, we found a biological signal that appears to be involved in how the disease starts and progresses,” Singh said. “That gives us a much better target for developing a therapy that is based on the disease mechanism itself.”
The team is now developing a new small-molecule therapy that eliminates the disease-related protein. This approach may allow for more precise treatment at lower doses and reduce unwanted side effects.
Why This Approach Is Different
Traditional drugs often lack specificity and are associated with off-target side effects, but the small molecules developed in Singh’s lab have the potential to be more precise, a characteristic that is especially useful for difficult-to-target disease drivers, such as sPLA2-IIA.
“We are trying to develop a therapeutic that can target the disease at an earlier stage and hopefully halt vision loss and perhaps improve vision” she said. “The hope is to shut down a harmful process at its source.”
A Grant Designed to Move Discovery Toward the Clinic
The project is funded through the NIH Blueprint Neurotherapeutics Network (BPN), a program that helps researchers advance promising small-molecule therapies from early discovery to clinical testing. Through this mechanism, the NIH provides scientific expertise and access to specialized consultants and contract research organizations that support key steps, including medicinal chemistry, pharmacokinetics, toxicology, formulation development, and early clinical planning.
If successful, the project could lead to a new way to treat AMD earlier, before major vision loss occurs, and may also help patients with related macular dystrophies that share similar disease features.
“Ultimately, our goal is to at least preserve vision and ideally improve vision,” Singh said. “If we can intervene earlier, we may be able to change the course of these diseases for many patients.”
