New approaches based on recent exciting advances in glycobiology provide the opportunity to develop novel and more effective classes of therapeutics, diagnostics, and functional foods to prevent or ameliorate major infectious and chronic disease worldwide.
The essential first step of any infection is binding by the pathogen to its host cell surface receptor, as illustrated at right. In many cases the critical determinant of binding is a specific carbohydrate moiety whose expression is typical of the target host cell. For enteric pathogens this critical moiety is found on the luminal surface of intestinal epithelial cells. For other pathogens the critical moiety is found on the surface of their specific target cell. In humans the target carbohydrate moiety critical for infection often terminates with a fucose and/or sialic acid sugar.
Certain complex carbohydrate molecules (oligosaccharides or glycoconjugates, collectively referred to as “glycans”), when taken orally can inhibit diarrhea caused by enteric (gut) pathogens. This is accomplished by competitive inhibition of pathogen binding. Glycans can also inhibit binding and infection by pathogens of respiratory, urinary, oral, and vaginal mucosa. Specific pathogens are inhibited by specific glycans, but some glycans inhibit multiple pathogens. Other glycans can be anti-inflammatory, modify metabolic development, and control adiposity. Glycosyn’s founding scientists are pioneers in an emerging new realm of academic research that is uncovering the roles of these glycans in fighting disease.
We have found that human milk, which contains thousands of bioactive glycans (including fucose and sialic acid-containing glycans), is particularly effective in preventing certain infectious diseases. These human milk glycans, when ingested orally, can protect against infection by numerous important enteric pathogens, including; Campylobacter jejuni, Vibrio cholerae, Escherichia coli and Norwalk virus. Moreover many milk glycans have specific additional functions that promote health. Over the past two decades the National Institutes of Health has sponsored research led by the Glycosyn team to identify bioactive glycans unique to human milk. Molecules have been discovered that are anti-infective, anti-inflammatory, and that promote mucosal development and immunity. These glycans, when produced commercially, will be the basis of novel therapeutic agents to promote healthy development and reduce risk of infection, inflammatory diseases, and adiposity.
For more detail, see J Biol Chem 2003, Glycobiology 2004, J Pediatr 2004, or Annu Rev Nutr 2005 (full citations in Publications).
Current therapeutic agents against diarrheal and other infectious diseases block pathogens’ growth and replication, but leave their environmental niches intact and thus set the stage for the development of resistant strains. This is a huge issue that impedes the broad use of conventional agents to prevent disease. In contrast, the bioactive glycans we are developing are based on natural protective molecules identified in human milk, against which pathogens over the millennia have been unable to develop resistance. Our molecules will be used broadly to prevent disease.
Although the potential use of glycans for improving health is extensive and highly promising, the lack of technologies for their efficient synthesis has limited their practical application. Glycosyn leads the way in developing novel methods for efficient synthesis of the most effective newly discovered therapeutic glycans and confirming their effectiveness in human populations. The Company’s ultimate goal is to bring to market promising novel classes of therapeutic agents, functional foods, and diagnostics based on these naturally occurring bioactive glycans.
Science
Many pathogens bind to specific glycans on their host cell surface receptors as their first step in pathogenesis.
Soluble glycans that terminate in the same sugars as the host receptors can bind to the pathogen, making the pathogen less able to bind to its host receptor.