Tuscany, Italy —Scientists met in Tuscany for the Gordon Research Conference (GRC) on Proteases, Inhibitors & Therapeutics to discuss new ways to understand and control proteases, enzymes that cut proteins and act as key regulators in processes ranging from immunity and blood clotting to infection, cancer spread, and inflammation.
If a protease contributes to disease, the obvious response is to block it, which is where protease inhibitors come in. But proteases are a classic example of why drug design is difficult; many proteases look similar to one another, and many are essential in healthy tissue.
The meeting aimed to connect basic researchers and drug developers working on protease biology, inhibitor design, and therapeutic strategies, with a particular emphasis on improving selectivity and safety.
Vinit Mahajan M.D., Ph.D., Stanford professor and vice chair of ophthalmology research, gave an invited lecture on proteases in age-related macular degeneration and possible drug targets.
He shared the lab’s novel liquid biopsy and proteomics platform that measures protease activity in the eyes of living patients, giving researchers validated targets for treatments.
Mahajan said, “As the only ophthalmologist and vision scientist at the meeting, I was excited to share our new method for measuring protease activity in patient eyes. Because proteases are central to so many processes, they show up repeatedly in many diseases. Understanding how to turn proteases on and off in one tissue could lead to big medical breakthroughs in another and save vision. We’ve taken our experience with calpain proteases in genetic eye disease and expanded our research into other retinal diseases where proteases play a role.”
Antoine Dufour Ph.D., professor in the Departments of Physiology & Pharmacology and Biochemistry & Molecular Biology and scientific director of the Southern Alberta Mass Spectrometry (SAMS) core facility at the Cumming School of Medicine, University of Calgary, shared his research on gut proteases in the colon.
Dufour explained, “The challenge is making an inhibitor that is selective, safe, and effective in the right place at the right time. That is why modern “protease therapeutics” increasingly includes approaches beyond simple blocking, such as designing inhibitors that avoid off-target effects, developing therapies that are activated only in certain environments like inflamed tissue or tumors, and improving ways to measure protease activity in living systems to guide treatment and patient selection.”
Sessions and poster discussions focused on mapping protease-driven signaling networks, measuring protease activity in realistic biological settings, and translating mechanistic insights into medicines, including next-generation inhibitors and approaches that localize or conditionally activate treatments to reduce side effects.
Mahajan said, “The conference met its goal of bringing together specialties across chemistry, biology, and medicine to share perspectives on inhibitor design, protease function in tissues, and patient needs. And in the spirit of the Gordon Conferences, people openly shared their most recent, unpublished data. This accelerates progress toward better drugs to control protease-driven disease processes without disrupting healthy ones.”