UNITY Biotechnology, Inc. announced new research published in the peer-reviewed journal Nature Medicine that supports the clearance of senescent cells in the retina as a therapeutic approach that can lead to long-term improvements in vision in patients with diabetic macular edema (DME). Sustained hyperglycemia from diabetes induces cellular senescence which damages the retina, including the delicate vasculature in the eye. This can lead to fluid accumulation and retinal thickening ?

a key feature of DME. The study shows that the therapeutic clearance of senescent cells can potentially remove an underlying source of pathogenesis and thus allow healthy cells to regenerate and remodel retinal vasculature, ultimately leading to long-term disease modification. Multiple studies have demonstrated that cells enter a state of senescence, in which they remain viable and metabolically active in the body, yet generate various inflammatory factors and metalloproteases.

These senescent cells can modify the surrounding environment and contribute to different cellular dysfunction and tissue degeneration. A team of scientists at University of Montreal and UNITY Biotechnology revealed that cellular senescent pathways are triggered in the diabetic retina and are specifically activated in endothelial cells. They demonstrated that these senescent cells contribute to loss of barrier function, which can cause leaky blood vessels.

Researchers showed that senolysis through BCL-xL inhibition improved retinal barrier function in diabetic mice, modifying the retinal microenvironment and reestablishing tissue homeostasis. In addition, in clinical trials BCL-xL inhibition led to improvements in visual acuity and retinal structure stabilization in patients with advanced disease. The BCL-xL inhibitor UBX1325 has been evaluated in a Phase 2 study as well, as previously announced, which demonstrated that a single injection led to statistically significant and clinically meaningful improvements in visual acuity through 48 weeks in patients with DME, while reducing anti-VEGF treatment burden.

UNITY is actively enrolling patients for a Phase 2b clinical trial where UBX1325 is being evaluated head-to-head versus aflibercept, with 16-week results expected in fourth quarter of 2024.