New antibody therapies may improve diabetic retinopathy and other eye conditions

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Professor Stephen Anger and Professor Sachidev Sidu took pictures at the Donnelly Center before the COVID-19 pandemic.Credits: University of Toronto

Insulin, a life-saving diabetes drug developed at the University of Toronto 100 years ago, was the first biotherapy and protein to treat the disease. A century later, new biological therapies developed by researchers at the University of Toronto have the potential to reverse the common complications of diabetes.

A team led by Professor Stephen Angers of the Faculty of Pharmaceutical Sciences Leslie Dunn, Vice Dean of Research, and Professor of Molecular Genetics at the Donnelly Cell and Biomolecule Research Center has developed synthetic antibodies as a promising treatment for diabetics. .. Retinopathy causes blindness and affects about 30% of diabetics.

Researchers tested antibodies on both Cell culture And the mouse, and the diary EMBO molecular medicine We announced the results today.

“This study shows that these are antibody A very attractive remedy for restoring the blood retina barrier “It gives new hope for the treatment of eye diseases such as diabetic retinopathy and macular degeneration,” said Rony Chidiac, a postdoctoral fellow in the Angers lab and the lead author of the study.

Angers and his team are experts in the Wnt cell signaling pathway, which is essential for the formation and maintenance of the blood-retinal barrier, a physiological barrier that prevents molecules from entering the retina.

Blood vessels leak and damage the eye when signal transduction pathways that can occur in rare eye conditions such as Norrie disease or when tissues are deficient in oxygen, such as diabetic retinopathy, are interrupted. May cause.

In a previous study, Angers worked with Sidu at the Donnelly Center to develop a catalog of synthetic antibodies that can activate Wnt signaling.

In their new publication, a method of activating one of the antibodies, specifically the Frizzled4-LRP5 receptor complex, successfully stimulated Wnt signaling at the blood-retinal barrier and effectively restored barrier function. Explains how.

Antibodies attach to two key cell surface receptors (Frizzled4 and LRP5) and bring them closer together, and this induced proximity activates the Wnt pathway that maintains blood vessels.

The team first tested the antibody in cell culture and found that it was a very accurate way to trigger signaling pathways and restore barrier function. They then worked with Harald Junge of the University of Minnesota and AntlerA Therapeutics, a startup founded by Angers and Sidhu, to test antibodies in a variety of mouse models. One model represented hereditary eye conditions and one model represented diabetic retinopathy.

Surprisingly, the antibody restored the barrier function of these mice and corrected retinal angioplasty.In addition, it’s new Blood vesselsLeakage of the blood-retinal barrier is one of the consequences of further eye damage.

With promising preclinical results of antibodies, AntlerA Therapeutics is now leading the transformation into commercialization and clinical research.

Although current research results focus on eye conditions, the similarities between the blood-retinal and blood-brain barriers mean that their application is much broader than eye conditions.

“The retinal vasculature was the first indication, and new funding was available to investigate the role of this pathway in other situations,” said Angers. For example, we are testing whether this antibody can affect the blood-brain barrier and whether it can repair the blood-brain barrier in the context of stroke.

“We had the opportunity to take action and found a way to activate Wnt signaling very accurately to actually treat these diseases,” Chidiac added. “We expect this to have a significant impact on various uses in regenerative medicine.”


Discovery of new drug for diabetic retinopathy


For more information:
Rony Chidiac et al., A Norrin / Wnt surrogate antibody stimulates the barrier function of endothelial cells and relieves retinopathy. EMBO molecular medicine (2021). DOI: 10.15252 / emmm.202113977

Quote: New antibody therapy may restore diabetic retinopathy and other eye conditions (10 June 2021) 10 June 2021, https://medicalxpress.com/news/2021- 06-antibody-therapy-reverse-diabetic-retinpath.html

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