Non-human sugar in biotech drugs causes inflammation

Researchers at the University of California, San Diego School of Medicine have discovered that a kind of sugar molecule common to chimpanzees, gorillas and other mammals but not found in humans, provokes a strong immune response in some people, likely worsening conditions in which chronic inflammation is a major issue.

This non-human sialic acid sugar is an ingredient in some biotechnology drugs, and may be limiting or undermining their therapeutic effectiveness in some patients, the scientists report in a letter published in the advance online July 25 edition of the journal Nature Biotechnology. However, they also propose a simple modification to the drug-making process that could solve the problem.

The presence of the non-human sialic acid sugar contaminant, called N-glycolyneuraminic acid or Neu5Gc, has long been known but ignored because it was believed healthy human immune systems did not react to it, said Ajit Varki, MD, professor of medicine and cellular and molecular medicine at UC San Diego School of Medicine. ''Now we know that to be untrue.''

''We're all exposed to this non-human sugar,'' Varki added. ''It's part of our diet, and especially abundant in red meat. We all develop antibodies to Neu5Gc, but this immune response varies greatly in people. Meanwhile, Neu5Gc from animal foods can get incorporated into the human body. For most people, this may not be a problem. But for some, the immune response to incorporated Neu5Gc may exacerbate a chronic inflammation process. This isn't the cause of any disease or condition, but we believe it might be akin to adding fuel to an existing fire.''

Every animal cell is cloaked in sugar molecules, which serve as vital contact points for interaction with other cells and their surrounding environment. At the same time, the attached sugars are targets for infectious diseases like influenza, malaria and cholera.

''Sialic acids are required for survival, but they're also used to attack you,'' said Varki, who is founder and co-director of the Glycobiology Research and Training Center at UC San Diego. ''They are crucial for things like brain plasticity and kidney function, but lots of pathogens attach to them, and some even coat themselves with these sugars to avoid detection. In evolutionary terms, if you have sialic acid, you're going to be attacked. But you don't have it, you're going to die.''