This bifunctional fusion protein resets the immune system to promote healthy tissue function by anchoring enzymes to the site of inflammation. Biologic drugs used to treat inflammatory diseases are a market that exceeds $30 billion annually. Available treatments to suppress inflammation are systemic, affecting unintended tissue and causing significant side effects. Localizing immunosuppressive drugs to sites of inflammation eliminates those problems.
Researchers at the University of Florida have developed a new approach to localize immunosuppressive enzymes to sites of inflammation. This technology platform is known as Galectin Anchors for Therapeutic Enzyme Retention. Specifically, they create a bifunctional fusion of an enzyme and galectin-3, a protein that binds to sugars decorating every tissue in our bodies. By binding to tissue sugars, Galectin-3 anchors the enzyme at the injection site. This prevents enzyme diffusion into surrounding tissue or entry into circulation. Their data show anchored enzyme formulations that persist at sites of inflammation for up to 2 weeks. Anchoring enzymes at the site of inflammation eliminates the side-effects that result from systemic distribution of drugs throughout the entire body.
The immunosuppressive enzyme utilized is indoleamine 2,3-dioxygenase (IDO), which breaks down the essential amino acid tryptophan into kynurenines. IDO naturally regulates the immune system in various contexts. For example, IDO establishes local maternal tolerance to the fetus to protect from immune attack without increasing host vulnerability to infection. Our bifunctional fusion protein resets the immune system to promote healthy tissue function by anchoring IDO to the site of inflammation, where it is administered. Restricting distribution of IDO avoids off-target side-effects and systemic immunosuppression.
Bifunctional fusion protein of galectin-3 and indoleamine 2,3-dioxygenase locally suppress inflammation
The bifunctional fusion protein, Gal3-IDO binds to tissue glycans to anchor the immunosuppressive enzyme at sites of inflammation. The inventors have demonstrated in in vivo models of osteoarthritis that Gal3-IDO can reduce inflammation, relieve pain, and restore gait. The inventors have demonstrated in in vivo models of periodontal disease that Gal3-IDO- can reduce inflammation and prevent the bone loss that leads to the need for tooth extraction. The inventors have demonstrated in in vivo models of bacterial endotoxin challenge that Gal3-IDO can shut down inflammation locally without systemic suppression.
