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New Technique is Softening Up a Tough Disease
Medical School genetic research on scleroderma featured at UT System Symposium
Using a new lab technique to tone down expression of a single gene, University of Texas Medical School at Houston researchers have found a potential soft spot in an incurable autoimmune disease that plagues patients by hardening tissue.
Frank Arnett, M.D., holder of the Elizabeth Bidgood Chair in Rheumatology at the UT Medical School at Houston, was among the speakers at the UT System Molecular Medicine Symposium.
Photo by Bill Olive
Frank Arnett, M.D., holder of the Elizabeth Bidgood Chair in Rheumatology, reviewed his team's innovative attack on scleroderma during a molecular medicine symposium sponsored in Houston by The University of Texas System Feb. 21-22.
He described the hunt for genes involved in scleroderma and subsequent employment of RNA interference (RNAi) to "knock down" activity of the SPARC gene.
"We found that knocking down SPARC knocks down production of collagen, and that's important, because collagen buildup causes scleroderma," Arnett said.
Scleroderma afflicts 300,000 Americans, 75 percent of whom are women, and in its most aggressive form kills half of patients within a decade of diagnosis. So far, only symptoms, not the disease itself, can be treated.
The team's research, published in the journal Arthritis and Rheumatism most recently in January, points to a potential therapeutic pathway for targeting the disease itself.
Having identified a variation of SPARC (secreted protein, acidic and rich in cysteine) in 2002 as raising a person's susceptibility to scleroderma, the team then applied small pieces of RNA to cultured human fibroblasts to reduce or even silence the gene's ability to create the SPARC protein.
Fibroblasts are precursors of connective tissue, such as collagen, which essentially binds body parts together. Expression of the SPARC gene and of type 1 collagen was cut in half in fibroblasts treated with RNAi targeted at SPARC.
The research team will next test the effect of RNAi in sclerodermic tissue. The team includes Xiaodong Zhou, M.D., assistant professor of internal medicine/rheumatology, and Filemon K. Tan, M.D., Ph.D., associate professor of internal medicine, as well as scientists from the laboratory of Dianna Milewicz, M.D., Ph.D., head of the Division of Medical Genetics and holder of the President George H. W. Bush Chair in Cardiovascular Medicine. Tan and Milewicz also hold faculty appointments in the UT Graduate School of Biomedical Sciences at Houston.
By Scott Merville, Public Affairs