Novel Antibody-Based Agonist for Neovascular AMD

This project aims to examine the efficacy of a novel synthetic antibody to protect from pathological new blood vessels growth and preserve vision in patients with AMD. We have engineered a novel synthetic antibody modality that protects against aberrant retinal vascular growth in diabetic retinopathy animal models. To translate our antibody towards clinical application for wet AMD or neovascular AMD, we aim to characterize the functional signaling induced by our novel antibody treatment in cellular models of relevance to AMD. Also, we will assess the efficacy of our molecules to promote the formation of healthy blood vessels and normalizing the growth of leaky altered vasculature in animal models mimicking the AMD disease.

Neovascular age-related macular degeneration (nAMD) is caused by the formation of new leaky and abnormal blood vessels that can lead to loss of vision. The common therapies for nAMD are injections of angiogenesis inhibitors into the eye with photodynamic therapy or laser surgery. These interventions can slow the progression of the disease but do not cure nAMD. Defective Wnt signalling pathway leads to leaky blood vessels. Activating Wnt signaling may be a viable therapeutic opportunity but is complicated by the existence of 19 Wnt proteins that can bind and activate 10 proteins on the surface of the cell called receptors with different responses. We engineered a novel molecule that can specifically activate one or multiple receptors mimicking Wnt proteins. For the first time, we were able to precisely activate one receptor and study its role in blood vessel formation and integrity. We found that our specific molecule restores vascular leakage and corrects retinal blood vessel formation in animals where the retinal vasculature is impaired. We aim to test the therapeutic potential of our molecule in models mimicking the nAMD disease. These synthetic agonists are attractive therapeutic modalities to control the formation of new blood vessels during nAMD.

We developed a novel antibody modality that allow us to activates one receptor of the Wnt/ßcatenin signaling pathway and have shown good efficacy in protecting against retinal vascular impairment. These molecules are attractive therapeutic modalities and could be a new class of drugs against pathological leakage of new blood vessels growth during AMD. Our proposed treatment strategy has the potential to not only reduce the burden of AMD disease, but to unleash the restorative power of the body’s own cells to repair defective and leaky blood vessels.

Our novel antibodies may hold new hopes for the treatment of neovascular AMD (nAMD). This proposal will enable us to advance this therapeutic candidate through preclinical studies and enable our long-time goal of testing our modality in clinical trial in nAMD patients. Treatment with these antibodies could actively repair the vascular tissue and could yield significant improvements in visual acuity or cessation of disease progression.