SAN DIEGO Department of Veterans Affairs (VA) researchers and colleagues have discovered a biochemical mechanism that may explain wasting syndrome, a condition that causes severe weight loss and weakness in patients with chronic inflammatory diseases and often hastens their death.
The findings, published in the December 3 issue of the European Molecular Biology Organization Journal, may lead to new drugs to ease the debilitating effects of cancer, AIDS, and other serious degenerative illnesses.
Scientists in San Diego pinpointed the biological chain of events that caused wasting in mice, then identified the same process in liver tissue from cancer patients.
They said the striking similarity between the condition in mice and humans will expedite the development of new treatments.
"When we saw that it was virtually identical in animals and humans, we were ecstatic," said the studys senior author, Mario Chojkier, M.D., of the VA San Diego Healthcare System and the University of California, San Diego (UCSD).
"What weve described in animals has much greater relevance than we ever thought to human wasting syndrome. Were optimistic this will bring hope and relief very quickly to the bedside."
Dr. Chojkier and lead author Martina Buck, Ph.D., of VA, UCSD and the Salk Institute for Biological Studies, described the steps by which tumor necrosis factor (TNF) alpha, an immune-system protein, prevents the production of albumin. Low levels of albumin, a critical protein made in the liver, is a keynote of wasting.
TNF-alpha and low albumin had for years been implicated in wasting, but the connection between the two was a mystery. Drs. Buck and Chojkier showed that TNF alpha causes oxidative stress in the liver cell and boosts the production of the free-radical gas nitric oxide. It also causes the addition of a phosphorous molecule to a protein called C/EBP beta, which normally joins DNA in the nucleus of the
Contact: Cindy Butler
VA Research Communications Service