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New Research Unveils ApoM as Key to Treating AMD and Heart Disease
A groundbreaking study from Washington University School of Medicine in St. Louis has identified a promising new therapeutic target for age-related macular degeneration (AMD), a leading cause of blindness in individuals over 50. The findings, published June 24 in Nature Communications, could pave the way for novel treatments for AMD and possibly some forms of heart failure, by addressing disruptions in cholesterol metabolism.
Researchers pinpointed apolipoprotein M (ApoM), a molecule associated with “good cholesterol,” as a potential key to slowing or halting AMD progression. Working with human plasma samples and mouse models, scientists discovered that boosting levels of ApoM corrected dysfunctional cholesterol processing and reduced cellular damage in the retina and heart.
“Our study points to a possible way to address a major unmet clinical need,” said senior author Rajendra S. Apte. “Current therapies that reduce the chance of further vision loss are limited to only the most advanced stages of macular degeneration and do not reverse the disease. Our findings suggest that developing treatments that increase ApoM levels could treat or even prevent the disease and therefore preserve people’s vision as they age.”
In dry AMD, the most prevalent form, cholesterol-rich deposits trigger a gradual breakdown of cells in the retina, akin to neurodegeneration seen in Alzheimer’s disease. These changes can evolve into the more severe “wet” form, characterised by abnormal blood vessel growth and rapid vision deterioration. Current treatments for advanced AMD manage symptoms but do not reverse the disease.
The study revealed that ApoM levels are significantly lower in patients with AMD compared to healthy individuals. A similar trend was found in patients with heart failure, suggesting a shared pathway involving cholesterol metabolism. ApoM, when bound to the signaling molecule sphingosine-1-phosphate (S1P), activates a protective cascade that helps break down cholesterol in lysosomes, the cellular "recycling centers", and curbs inflammation.
By increasing ApoM in mouse models through genetic enhancement or plasma transfer, the team observed improved retinal function and a reduction in harmful cholesterol buildup.
The team is now working with Mobius Scientific, a startup launched out of Washington University in 2022, to translate these findings into clinical applications. The company, in collaboration with the university’s Office of Technology Management, is exploring ways to harness ApoM-based therapies for AMD and cardiovascular disease.
“One of the exciting things about this collaboration is realizing the links between retinal pigment epithelial cells and heart muscle cell, which are both vulnerable to low ApoM,” co-senior author Javeheri said. “It is possible that the interaction between ApoM and S1P is regulating cholesterol metabolism in both cell types. We look forward to exploring strategies to increase ApoM in ways that could help the eye and the heart maintain healthy cholesterol metabolism over time and stave off two major diseases of aging.”
(Photo: color-stained retinal epithelial cells from a mouse eye. Credit: Tim Lee/WashU Medicine)
