MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2

Abstract

Diabetes is an incurable, chronic disease that can lead to many complications, including angiopathy, peripheral neuropathy, and erectile dysfunction (ED). The angiopoietin-Tie2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve regeneration. Therefore, strategies for activating the Tie2 signaling pathway have been developed as potential therapies for neurovascular diseases. Here, we developed a human Tie2-agonistic antibody (MT-100) that not only resists Ang-2 antagonism and activates Tie2 signaling but also regulates a novel target, sushi repeat-containing protein X-linked 2 (Srpx2). This regulation led to the survival of vascular and neuronal cells, a reduction in the production of reactive oxygen species (ROS), activation of the PI3K/AKT/eNOS signaling pathway, increased expression of neurotrophic factors, and ultimately alleviation of ED in diabetic mice. Our findings not only provide conclusive evidence that MT-100 is a promising therapeutic strategy for the treatment of diabetic ED but also suggest it has substantial clinical applications for other complications associated with diabetes. Erectile dysfunction is a condition where men have difficulty maintaining an erection. It is common among men with diabetes, often due to severe damage to blood vessels. Researchers found a need for better therapies for diabetic ED. They created a new humanized antibody, MT-100, which targets the Tie2 receptor. The Tie2 receptor is important for keeping blood vessels stable and protecting nerves. In their study, they tested MT-100 on diabetic mice. After injecting MT-100, the mice showed better erectile function due to improved blood vessel and nerve growth. MT-100 also helped cells survive and reduced oxidative stress, which is damage caused by harmful molecules. The study suggests MT-100 could be a promising treatment for diabetic ED by supporting blood vessel and nerve health. Future studies might look at MT-100 for other blood vessel diseases. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.