Reviewed by Emily Henderson, B.Sc
An international team of researchers led by Baylor College of Medicine and Houston Methodist has discovered a strategy that can potentially address a major challenge to the current treatment for choroidal neovascularization (CNV), an aggressive form of age-related macular degeneration, the leading cause of irreversible blindness in the elderly.
Anti-vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment for CNV; however, up to one-fourth of all treated patients are unresponsive to this treatment and about one-third of the responders become resistant to it after repeated administration over time.
Working with a mouse model they developed, the researchers found that combining apolipoprotein A-I binding protein (AIBP) with anti-VEGF overcomes anti-VEGF resistance and effectively suppresses CNV. The findings open the possibility of reducing anti-VEGF resistance in patients in the future. The study appears in the journal Communications Biology.
Addressing resistance to anti-VEGF treatment has been challenging. For instance, developing strategies to overcome the resistance has been limited by a poor understanding of its mechanism and the absence of suitable animal models.
Various combination therapies have been explored in clinical trials. For example, targeting PDGF (Fovista) or the angiopoietin pathway. However, no major breakthrough has been reported. In fact, a phase III trial combining anti-VEGF and PDGF failed to demonstrate improved efficacy.”
Dr. Yingbin Fu, co-corresponding author, associate professor and Sarah Campbell Blaffer Endowed Chair of Ophthalmology at Baylor
A new approach to combat anti-VEGF resistance
Fu joined forces with Dr. Longhou Fang, associate professor of cardiovascular sciences at Houston Methodist DeBakey Heart and Vascular Center and co-corresponding author of this work.
The inspiration for their study came from previous work suggesting that macrophages may play a role in anti-VEGF resistance and that increased cholesterol accumulation in macrophages may promote CNV. Such cholesterol accumulation also has been associated with the formation of abnormal new blood vessels invading the retina. These vessels leak, which promotes inflammation and rapid photoreceptor (light-detecting cells) damage…..
Source: News Medical Life Sciences