Nov. 3, 2000 (Philadelphia) -- With all the advances in medicine, one disease that has defied researchers has been a condition called scleroderma, which can cause significant disability, and possibly death in those affected. Now the enzyme causing it has been identified, and investigators hope that they also have identified a way to suppress this enzyme, and therefore, to treat this baffling disease.
The disease occurs because the body produces excessive amounts of collagen, a tough substance that is normally present in the body's connective tissue, such as tendons and cartilage. Collagen also promotes scarring, though, and the excessive collagen production that is characteristic of scleroderma causes the body to also produce excessive scar tissue.
Scleroderma literally means "hard skin," and in localized scleroderma, the skin is the primary affected organ. The more severe form of the illness, systemic sclerosis, affects several internal organs and can be fatal.
At present, the only treatment of scleroderma is treatment of some of the symptoms; progression of the illness cannot be halted. However, the missing piece of the puzzle may have been found in an enzyme that triggers the excessive collagen and scar tissue, according to Sergio Jimenez, MD, speaking here at the annual meeting of the American College of Rheumatology.
"The public needs to know that scleroderma is a very severe disease, more severe in its mortality rate than breast cancer," Jimenez tells WebMD. "In our study, we have identified the cells responsible for collagen overproduction and subsequent scar tissue, and we have identified a substance that was able to suppress collagen production in cells in the laboratory setting." Jimenez is the Dorrance H. Hamilton professor of medicine at Jefferson Medical College of Thomas Jefferson University here, where he also is a professor of both biochemistry and molecular pharmacology.
In laboratory studies, Jimenez and colleagues identified the enzyme, an offshoot of what's known as protein kinase C, and they also may have identified a substance that suppresses this enzyme. If these initial laboratory studies of scleroderma cells hold true in trials of animals and later humans, a treatment for scleroderma eventually may be developed, he says.
The enzyme regulates the rate at which the body produces collagen. It is relatively inactive in healthy people and three to four times as active in people with scleroderma, Jimenez says.
After identifying the enzyme, he and co-investigators sought to determine whether a substance that suppresses the enzyme, called rottlerin, would block the genes that produce collagen in cells. They found that collagen production was inhibited 70% to 85%, and the levels of the collagen gene were reduced 80% to 95%. On the other hand, levels of other substances typically found in cells were unchanged.
Because of these findings, Jimenez and colleagues are hopeful that these currently untreatable conditions may have found their match. However, the potential treatment's journey down the path from the laboratory to the clinic, and to improvement in the lives of scleroderma patients, has just begun.
"We're extremely encouraged," he tells WebMD. "The next step is animal testing, and if the findings hold true, we may be on the way to developing a treatment for scleroderma. The idea of being able to help these patients is very exciting."