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Gene therapy reduces skin cancer to sunburn in mouse model

DALLAS Dec. 10, 2004 Researchers at UT Southwestern Medical Center at Dallas have successfully tested the first gene therapy for skin cancer, using a mouse model for the disease xeroderma pigmentosum, or XP.

Their results, available online and to be published in an upcoming issue of the Proceedings of the National Academy of Sciences, show promise for similar gene therapy to be pursued in children suffering from this rare disorder.

XP is a debilitating disease in which patients must avoid the sun and all other sources of ultraviolet (UV) light. Exposure to UV light increases the risk for all cancers, but exposed skin is most prone to the disease.With a 10,000-fold increase in cancer risk, many XP sufferers eventually succumb to tumors at an early age.

Mice with mutations in the gene Xpa suffer from XP and develop cancerous lesions on their skin within three weeks after UV light exposure. Dr. Errol Friedberg, professor and chair of pathology at UT Southwestern, in collaboration with Dr. Carlos F.M. Menck of the Institutes of Biomedical Sciences in Sao Paulo, Brazil injected the normal gene into mice suffering from XP. After treatment with the normal gene, the mice were free from disease.

"Gene therapy for XP has the potential to completely prevent cancer in a group of patients who otherwise may suffer no other ill effects from their genetic defect," Dr. Friedberg said.

When the body is exposed to UV light, the DNA in dividing cells can become damaged. Normally, the body enlists a group of proteins whose job it is to repair the sites of UV-induced damage. But in children with XP, mistakes in DNA caused by UV light cannot be fixed because of mutations in the genes for the repair proteins. DNA damage goes uncorrected, and as cells divide they accumulate numerous mutations. When these mutations occur in genes that normally suppress cancer, cells develop abnormally and cancer ensues.

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Contact: Megha Satyanarayana
megha.saty@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
9-Dec-2004


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