If there is a strong antibody response to diet-incorporated Neu5Gc, the resulting inflammation could cause harm to the person. This may partially explain associations between certain foods and increased risk of diseases associated with inflammation, such as cancer and heart attacks - diseases that are rare in other primates.

The problem may also be exacerbated by the presence of Neu5Gc in drugs developed through recombinant biotechnology, some of which are actually used to treat inflammatory disorders. Neu5Gc contamination is unavoidable with current methods, said Varki, because many biotherapeutics such as antibodies, clotting factors or hormones are produced using cells, tissues or serum from mammalian sources, which naturally contain the non-human sialic acid.

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.

They also report that anti-Neu5Gc antibodies from normal humans interacted with a Neu5Gc-containing drug used to treat some forms of cancer, producing immune complexes in vitro. Mice with a human-like defect in Neu5Gc synthesis also generated anti-Neu5Gc antibodies when injected with the drug, and cleared it from the circulation faster. These problems were not seen with another otherwise similar drug, which happened to be practically free of Neu5Gc.

"It's reasonable to suggest that for some patients who have problems with some drugs, this may be part of the reason why," although a lot more needs to be done to work out the details," Varki said.

Meanwhile, the UCSD scientists have developed a novel yet simple solution: Add the human sialic acid 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."

Source : Nature Biotechnology

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