The chemotherapy drug paclitaxel, when given to mice, shows signs of impeding the skin disease scleroderma, researchers report. By slowing skin thickening, paclitaxel might offer a treatment for a disease that has defied cure.
Scleroderma results when excess collagen protein accumulates in the skin, rendering it fibrous and inflexible. This toughening can cause pain and disfigurement. In some patients, collagen collects in the blood vessels, heart, or lungs, any of which can be lethally damaged. Scleroderma seems to stem from an immune backlash against the body's own tissues, although what triggers the disease is unclear.
Cardiologist Pascal J. Goldschmidt-Clermont of Duke University School of Medicine in Durham, N.C., and his colleagues became interested in paclitaxel, marketed as Taxol, because previous experiments had indicated that the drug could stabilize microtubules--tiny conveyor belts in cells that normally help them function. The researchers had suspected that destabilized microtubules trigger a process that activates the protein TGF beta, a growth factor that stimulates cells to produce excess collagen.
To test whether calming microtubules with paclitaxel would fight collagen buildup, Goldschmidt-Clermont and his team transplanted skin grafts from people with scleroderma into mice. Some transplants were first soaked in paclitaxel, while others weren't. The treated grafts produced significantly less collagen than did the untreated grafts, the researchers report in the December PLoS Medicine.
Paclitaxel also inhibited the activity of TGF beta, the new data suggest.
"This is an intriguing study," says John Varga, a rheumatologist at the Northwestern University School of Medicine in Chicago. In scleroderma research, "targeting TGF beta is where the action is." But Varga cautions that the study is preliminary. "To extrapolate from this mouse model to human scleroderma is hard," he says.
The study authors acknowledge that paclitaxel has one troubling effect. In some cancer patients, it actually causes collagen buildup in the skin. While that risk needs to be further investigated, Goldschmidt-Clermont says, the amount of paclitaxel used in these skin grafts was proportionately much less than that used in patients receiving it as chemotherapy.
Although some drugs can ease lung complications in scleroderma patients, "there isn't any one drug available that treats the disease overall," says Carolyn Weller, vice president of education and research at the Seleroderma Foundation in Danvers, Mass.
If further research indicates a benefit from paclitaxel in people, it would join two other cancer drugs--imatinib mesylate (Gleevec) and rituximab (Rittuxan)--being investigated for use against scleroderma.
Roughly 300,000 people in the United States have scleroderma.
COPYRIGHT 2005 Science Service, Inc.
COPYRIGHT 2005 Gale Group
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