Non-human sugar in drugs causes chronic inflammation
July 26th, 2010 - 4:50 pm ICT by ANILondon, July 26 (ANI): Scientists have discovered that a kind of sugar molecule found in some biotechnology drugs may limit or undermine their therapeutic effectiveness in some patients leading to chronic inflammation.
The sialic acid sugar common to chimpanzees, gorillas and other mammals but not found in humans provokes a strong immune response in some people.
However, a simple modification to the drug-making process 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 of University of California.
“Now we know that to be untrue,” Nature quoted Varki as saying.
“We’re all exposed to this non-human sugar. 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.
“For some people, 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.
“Sialic acids are required for survival, but they’re also used to attack you,” said Varki.
“They are crucial for things like brain plasticity and kidney function, but lots of pathogens attach to them.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,” he added.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.
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,” he said.
The findings were published in the online edition Nature Biotechnology. (ANI)
- How eating red meat, milk can promote increased cancer spread risk - Nov 14, 2008
- Missing sugar molecule 'increases diabetes risk' - Feb 25, 2011
- Why eating red meat may be hazardous for your health - Oct 30, 2008
- How cholera bug invades the gut - Jan 29, 2012
- Molecular changes that helped Tamiflu resistance explained - Jun 04, 2010
- Now, cheap, efficient method to convert algae into renewable fuel - Mar 06, 2011
- Aspirin could compromise effectiveness of vaccines - Dec 02, 2009
- Gene that controls immune system linked to preeclampsia - Feb 15, 2011
- Why so many antibodies turn out to be ineffective in blocking HIV infection - Nov 19, 2010
- Decrease in protein levels could be sign child will develop diabetes - Apr 26, 2011
- Omega-3 eases anxiety among young - Jul 14, 2011
- Defects in immune system enzyme 'raise arthritis, diabetes risk' - Jun 17, 2010
- How omega-3 fatty acids reduce inflammation - May 03, 2010
- Compound that effectively suppresses multiple sclerosis developed - Apr 19, 2011
- Amazing jab cuts down damage in heart attack by 60 percent - Apr 19, 2011
Tags: ajit varki, antibodies, biotechnology drugs, biotherapeutic agents, brain plasticity, chimpanzees, chronic inflammation, contaminant, evolutionary terms, gorillas, human immune systems, immune complexes, immune response, kidney function, mammals, neu5gc, red meat, sugar molecule, therapeutic effectiveness, vitro