SIALIC acid sugar, a non-human sugar found in pharmaceuticals produced using recombinant biotechnology, can provoke a strong immune response from some people, research has found.

The sugar, which occurs naturally in gorillas, chimpanzees and other mammals but not humans, had previously been thought to be safe for use in human medicines. However, researchers at University of California, San Diego, have found that while healthy humans do not normally react to this the situation is different for some, particularly patients suffering from chronic inflammation.

Ajit Varki, professor of medicine at UCDA and lead author of the study, says that while practically everybody is exposed to Neu5Gc – sialic acid sugar – through their diet (the sugar is particularly abundant in red meat) there is a great deal of variation in the level of immune response this triggers. “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," Varki says.

Because every non-human mammalian cell is coated in Neu5Gc molecules, the sugar is present in virtually all drugs developed through recombinant biotechnology, which employs mammalian cells, tissues or serum to produce biopharmaceuticals such as antibodies, clotting factors or hormones. Varki and colleagues studied several biotherapeutic agents currently in clinical use, and found the non-human sialic acid in almost all of them, although in varying amounts.

Trials on humans and mice that had been genetically engineered not to produce the Neu5Gc sugar showed that the compound can produce an immune response which can cause further complications for the patient, and also rapidly clears the pharmaceutical from the system

"It's reasonable to suggest that for some patients who have problems with some drugs, this may be part of the reason why," Varki says, though he concedes that more work is needed to understand the details.

Meanwhile, the UCSD scientists have developed a novel yet simple solution: Add the human sialic acid variant, Neu5Ac, to the drug-making process. The Ac version, said Varki, competes with the Gc version, reducing the chances of the Gc version making it into the final product.

"In our initial tests, it removes low-level Gc contamination in drugs," said Varki. "It's simple and should only require minor FDA approval for the process adjustment. We think that while we've identified a problem, we've also come up with an answer, at least for some drugs."

Nature Biotechnology DOI: 10.1038/nbt.1651