- ANTs are precision-engineered Antlera antibody therapeutics for regenerative medicine
SAN FRANCISCO, June 9, 2021 /PRNewswire/ -- AntlerA has applied its next generation programmable ANT platform to develop therapeutics for treating retinopathies.
Blood vessels that supply oxygen and nutrients to the retina are tightly sealed to ensure that they do not leak their contents into the retina. Retinopathy are a group of diseases where blood vessels in the eye become leaky causing damage to the retina, eventually leading to loss of vision. In a study published in EMBO Molecular Medicine, scientists from AntlerA, in collaboration with Drs. Sachdev Sidhu and Stephane Angers from the University of Toronto, and Dr. Harald Junge from the University of Minnesota Medical School, report the development of an antibody drug that mimics Norrin, a secreted protein, required for the maintenance of the blood vessel integrity in the eye.
"In 2019 in eLife we reported the development of an advanced protein-engineering technology platform that can be used to activate the Wnt/b-catenin signaling pathway precisely and on demand. Norrin signals through the Wnt cascade and making recombinant Norrin is not straightforward. It is exciting to see that the AntlerA team, building on our earlier studies, have developed a Norrin-mimetic antibody that has enormous clinical potential," said Dr. Sachdev Sidhu, Professor, University of Toronto and co-lead author on the study.
"The biology of the vascular barrier function is well worked out. Human and mouse genetic studies over the last two decades have established Norrin signaling to be important for maintaining the blood retinal barrier. Norrin binds to FZD4/LRP5 and activates signaling required for maintenance of the tight junctions between endothelial cells that line the retinal blood vessels. Loss of blood retinal barrier function is well recognized in diabetic retinopathy and other eye diseases. A Norrin-mimetic would be an excellent drug that can restore proper blood vessel function and improve vision. We were excited to find that the drug candidate worked very well in preventing pathological vascularization in a mouse model of human retinopathy of prematurity (ROP), a condition that affects over 14,000 premature infants in the US alone annually. In the blood vessels in the brain the same FZD4/LRP5 signaling, though mainly turned on by Wnt7a/b protein, is responsible for preventing the blood vessels from leaking. The AntlerA Norrin-mimetic has applications beyond the eye as a Wnt7-mimetic in areas such as stroke, age-related hearing loss and traumatic brain injury," added Dr. Stephane Angers, lead study author and Professor at the University of Toronto.
"The Norrin/Wnt7-mimetic actively promotes those blood vessel functions which prevent leakiness. We tested the AntlerA Norrin/Wnt7-mimetic in a genetic mouse model of retinopathy and found that the agonist rescued the vascular defects and also blocked the blood vessel leakage in this disease model," said Dr. Harald Junge, from the University of Minnesota Medical School and a co-lead author on the study.
"There is a significant unmet medical need in several rare pediatric retinopathies including FEVR/Norrie, Coats, and ROP, as there are no approved drugs for their treatment. Our Norrin/Wnt7-mimetic is an important drug candidate for these pediatric patients. Also, it will provide a new treatment modality for macular telangiectasia and diabetic retinopathy, which afflicts over 4 million people in the US alone. The mechanism of action of the drug is supported by strong human and mouse genetics and it acts by restoring signaling fundamental to junctional integrity of vascular blood vessels. We plan to bring this exciting drug to clinical trials rapidly," said Dr. Sekar Seshagiri, CEO of AntlerA Therapeutics.
AntlerA Therapeutics is a regenerative medicines company focused on developing novel protein therapeutics that function by modulating Wnt signaling to harness the regenerative potential of tissue resident stem cells.