A Synthetic Norrin/Wnt Antibody Restores Blood-Retina Barrier in Diabetic Retinopathy, in Mice

Article: U of T researchers develop antibody drug that could treat diabetic retinopathy
Source: University of Toronto (Canada)
Published: June 9, 2021

F4L5.13 partially restored blood-retina barrier function in mice

A team of researchers at University of Toronto are developing a new antibody as a potential treatment for diabetic retinopathy and other diseases caused by defects in the blood-retina barrier. Specifically, the researchers studied the Norrin/Wnt cell signalling pathway, which is crucial for the formation and maintenance of the blood-retina barrier. When this signalling pathway is disrupted, such as in diabetic retinopathy, the blood vessels become leaky, compromising the blood-retina barrier. The current publication describes how a synthetic antibody (F4L5.13) activating the Frizzled4-LRP5 receptor complex successfully stimulated Norrin/Wnt signalling to restore barrier function. This antibody activates the Norrin/Wnt pathway by attaching to two key cell surface receptors (Frizzled4 and LRP5) and bringing them into close proximity. The researchers have thus far tested their antibody in cell cultures and in two mouse models, one representing a genetic eye condition (for Norrie disease) and one for diabetic retinopathy. In the cell culture model, the antibody restored barrier function "in part by promoting surface expression of junction proteins." Treatment of the antibody in mice restored barrier function and "significantly normalized neovascularization in an oxygen-induced retinopathy." The investigators have founded a start-up company to proceed with translation of their work to clinical studies. One century ago in 1921, researchers at University of Toronto developed insulin, the life-saving medication to treat diabetes. It is especially fitting, therefore, that U of T researchers continue that legacy, in this case to develop a drug therapy for a common ocular complication of diabetes. Because of similarities between the blood-retina and blood-brain barriers, they also plan to extend their research to other contexts.

My rating of this study: ⭐⭐🌸

Chidiac R, Abedin M, Macleod G, et al. "A Norrin/Wnt surrogate antibody stimulates endothelial cell barrier function and rescues retinopathy." EMBO Molecular Medicine.  13:e13977. 9 June 2021. https://doi.org/10.15252/emmm.202113977