What is the mechanism of Conbercept?

Conbercept is a recombinant fusion protein used primarily as a therapeutic agent in the treatment of various ocular diseases, including age-related macular degeneration (AMD), diabetic macular edema (DME), and myopic choroidal neovascularization (CNV). Understanding the mechanism of Conbercept involves delving into its molecular structure, its interaction with specific targets, and its biological effects on the eye.

Conbercept's molecular structure is designed to inhibit the activity of vascular endothelial growth factor (VEGF), a protein that plays a critical role in the formation of new blood vessels (angiogenesis) and increased vascular permeability. Excessive VEGF activity is associated with pathological conditions in the retina, leading to vision loss and other serious complications.

The structure of Conbercept is engineered to be highly effective in neutralizing VEGF. It is a fusion protein that combines the second immunoglobulin (Ig) domain of VEGF receptor 1 (VEGFR-1) and the third and fourth Ig domains of VEGF receptor 2 (VEGFR-2) with the Fc portion of human immunoglobulin G1 (IgG1). This unique configuration allows Conbercept to bind to all isoforms of VEGF-A, VEGF-B, and placental growth factor (PlGF) with high affinity.

The mechanism of action begins with Conbercept binding to VEGF molecules. By capturing and sequestering VEGF, Conbercept prevents VEGF from interacting with its natural receptors on the surface of endothelial cells. Normally, the binding of VEGF to its receptors would trigger a cascade of signaling events that promote endothelial cell proliferation, migration, and new blood vessel formation. By blocking these interactions, Conbercept effectively inhibits these processes.

The inhibition of VEGF signaling by Conbercept has several therapeutic effects. Firstly, it reduces the abnormal growth of blood vessels in the retina and choroid, which is a hallmark of conditions like AMD and myopic CNV. Secondly, it decreases vascular permeability, thereby reducing fluid leakage and the resultant macular edema seen in diseases like DME. This reduction in fluid accumulation helps to restore normal retinal architecture and function, ultimately leading to an improvement in vision.

Furthermore, Conbercept's prolonged binding to VEGF allows it to have a longer duration of action compared to other anti-VEGF therapies. This means that patients may require fewer injections, enhancing their compliance and overall experience with the treatment.

In summary, Conbercept exerts its therapeutic effects by targeting and neutralizing VEGF, thereby inhibiting abnormal blood vessel formation and reducing vascular permeability in the retina. Its unique molecular design and high binding affinity for multiple VEGF isoforms contribute to its efficacy in treating various retinal diseases characterized by pathological angiogenesis and edema. Understanding this mechanism provides valuable insights into the treatment options available for patients suffering from vision-threatening conditions.