Ah, sugar, sugar

12/Mar/2015

Cubes of sugar. © HandmadePictures, Fotolia

Are we on the verge of a minor revolution in medicine? In recent years a new category of substances – largely unnoticed by the general public – has increasingly become the focus of research: so-called glycomimetics or ‘dummy sugars’. By Roland Fischer

(From "Horizons" no. 104, March 2015)

If you hear the word ‘carbohydrates’, you don’t automatically associate it with medical matters, but with your own energy balance. Yet sugars are not just burnt up in the human body to provide it with energy. They also play an important role in many biological processes, especially in the communication between cells. Long, often complex, ramified sugar molecules called oligosaccharides sit on the outer membranes and function like keys that can open up the corresponding locks – called lectins – on the surface of other cells. This then sets off a specific reaction. In this manner, carbohydrates play an important role in inflammatory responses, for example.

Their central role in many cellular processes ought to make sugar molecules ideal candidates for new medical agents. But there’s a problem with that, as Beat Ernst from the University of Basel explains. “When I talk about my research and my therapeutic ideas at conferences, I always get the same answer: sugar molecules are too different from classical medicines, which is why they’re not suitable for medication”. There are two reasons for this: first, sugar molecules are highly polar and so can’t get past membranes in the body. This in turn means that they can’t be given orally. You can only introduce them to the body intravenously, but the body then tries to get rid of them quickly. After a few minutes, most of the molecules administered have been eliminated from the body. The second big problem is their interaction with the corresponding ‘docking sites’ in the human body, for this interaction is often very weak when it comes to sugar molecules.

So is this a case of something being interesting in theory, but hopeless in practice? In fact, a minor pharmacological revolution gradually seems to be taking place. There are strong indications that sugar molecules could indeed be used as drugs in future. Thanks to a lot of patience and ingenuity, Ernst’s research group seems to have overcome both problems. Ernst is convinced that both the long wait and his tenacity will pay off in the coming years. “Research is a little bit like boxing”, he says, hinting at his many setbacks and his role as the research underdog. “You have to be able to take punches and, above all, you have to pull yourself up again if you’re knocked to the ground”.

A stir on the stock markets

How have the researchers managed this? The problem with the rapid elimination from the body was solved by a trick already proven effective for a tumour drug, while the weak interaction with the body’s docking sites has gradually been optimised up to the point where the first active substances can be sent for clinical trials.

Ernst and his research team have been working for 10 years with the company GlycoMimetics. They’re currently causing a stir on the stock markets because of their joint patent, Rivipansel, which is intended to treat sickle cell anaemia, and also because of their promising studies on leukaemia samples. Together with two colleagues, Ernst has recently also founded a company that intends to use dummy sugars for clinical applications against autoimmune diseases. In a further project, dummy sugars are being developed for use against cystitis instead of antibiotics. Ernst expects that their different mode of action will mean that these sugar agents will prove to have great advantages over antibiotics in matters of drug resistance.

Roland Fischer is a freelance science journalist.

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