Natural sugar ‘revs up’ immune response to atherosclerosis

While injected trehalose reduced the size of arterial plaques in mice, administering it orally and injecting other types of sugars had no effect.

Researchers from the Washington University School of Medicine found that injecting trehalose, a naturally occurring sugar, reduced arterial plaque in mice. They aim to create an oral version of the treatment for atherosclerosis.

Trehalose, which is found in plants and insects, boosts macrophage function, the team discovered. Macrophages are white blood cells responsible for engulfing and digesting microbes and cellular waste. But this process backfires in atherosclerosis.

“In atherosclerosis, macrophages try to fix the damage to the artery by cleaning up the area, but they get overwhelmed by the inflammatory nature of the plaques,” said Babak Razani, M.D., Ph.D., an assistant professor of medicine at Washington University, in a statement. “Their housekeeping process gets gummed up. So their friends rush in to try to clean up the bigger mess and also become part of the problem. A soup starts building up—dying cells, more lipids. The plaque grows and grows.”

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In the study, mice prone to atherosclerosis were injected with trehalose and had smaller plaques in the aortic root, the part of the aorta closest to the heart. Their plaques measured 0.25 square millimeters, while untreated mice had plaques measuring 0.35 square millimeters, a “statistically significant” difference. The results were published in Nature Communications.

Trehalose works by activating the protein TFEB, which moves into the nucleus of macrophages and binds to DNA there, the team said in the statement. This switches on some genes, which ultimately ramps up the “degradative capacity” of cells.

“Trehalose is not just enhancing the housekeeping machinery that’s already there,” Razani said. “It’s triggering the cell to make new machinery. This results in more autophagy—the cell starts a degradation fest.” However, it is unknown how trehalose boosts autophagy, or self-eating.

Taking trehalose orally does not prompt the same immune response because the body digests it. Injecting other types of sugar did not reduce the size of plaques either, according to the statement.

The team hopes to find a way to block the enzyme that digests trehalose, so that they can administer it orally.

Trehalose is FDA-approved for human consumption and is often used in pharmaceuticals. Bioblast has been working on an intravenous form of trehalose for the treatment of two rare degenerative conditions but has hit some roadblocks lately. The candidate showed some activity in phase 2a trials for oculopharyngeal muscular dystrophy and spinocerebellar ataxia type 3 but did not provide compelling evidence of efficacy.