Pathophysiology of heparan sulphate: many diseases, few drugs

Heparan sulphate (HS) polysaccharides are covalently attached to the core proteins of various proteoglycans at cell surfaces and in the extracellular matrix. They are composed of alternating units of hexuronic acid and glucosamine, with sulphate substituents in complex and variable yet cell-specific patterns. Whereas HS is produced by virtually all cells in the body, heparin, a highly sulphated HS variant, is confined to connective-tissue-type mast cells. The polysaccharides interact with a multitude of proteins, mainly through ionic binding, and thereby control key processes in development and homoeostasis. Similar interactions also implicate HS in various pathophysiological settings, including cancer, amyloid diseases, infectious diseases, inflammatory conditions and some developmental disorders. Prospects for the development of HS-based drugs, which are still largely unrealized, are discussed.