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Seminar

Thursday, June 13th, 2019
11h30
Centre de Recherche - Paris - Amphithéâtre Hélène Martel-Massignac

Galectins as targets for clinical therapy and diagnostics

Galectins are small soluble, often abundant, proteins with affinity for extracellular/intravesicular glycoproteins and glycolipids, but also have cytosolic and nuclear activities. Studies in animal disease models, including KO mice, and expression levels in human tissues have suggested rate limiting roles in cancer and inflammatory disease like fibrosis. Experiments in cell culture have provided some possible mechanisms of action, including regulation of receptor organization and residence time at the cell surface and effects on cell migration.

These findings have inspired development of galectin inhibitors as therapeutics, and galectins as part of diagnostics. Galectins have a well characterized about 135 amino acid carbohydrate recognition domain folded as a b-sheet. Galectins are druggable in the sense that it has been possible to design small molecule very potent inhibitors, even if the carbohydrate-binding site is relatively shallow. Such galectin inhibitors have shown promising effects in mouse models of cancer and also lung fibrosis. One molecule, TD139, is in phase II clinical development as an inhaled drug for idiopathic lung fibrosis.

The roles of galectins in disease can to some degree be related back to their roles in the cell, but not completely or in a simple way. This creates a challenge for defining mechanism of action of galectin inhibitors, and relevant aspects of pharmaco-kinetics and pharmaco- dynamics (PK/PD). At the same time galectin inhibitors can be seen as tools for deeper understanding of galectin function.

As diagnostics the level of galectin-3 in blood has found widespread use as a marker of cardiac insufficiency. Its level in thyroid tissue is also used to distinguish malignant from benignant tumors there. However, the level of specific galectin-binding glycoforms of common glycoproteins in serum may be an even more interesting diagnostic marker, and reflection of galectin function.

Speaker(s)

Prof. Hakon Leffler
Senior Professor in Sabbatical MAYENT ROTHSCHILD - Institut Curie
Domain 4 - UMR 3666 / U1143 - Chemical Biology of Membranes and Therapeutic Delivery

Institut Curie

Hosted by

Ludger Johannes
Domain 4 - UMR 3666 / U1143 - Chemical Biology of Membranes and Therapeutic Delivery

Institut Curie

Invited by

Dr. Ludger Johannes
Domain 4 - UMR 3666 / U1143 - Chemical Biology of Membranes and Therapeutic Delivery

Institut Curie