אסיף מאגר המחקר החקלאי

Effect of halofuginone on the development of tight skin (TSK) syndrome

Year:

2002

Source of publication :

Authors :

Volume :

35

Co-Authors:

Gaha, T.M.c., Department of Microbiology, Mount Sinai School of Medicine, Box 1124, One Gustave L. Levy Place, New York, NY 10029, United States
Kodera, T., Department of Microbiology, Mount Sinai School of Medicine, Box 1124, One Gustave L. Levy Place, New York, NY 10029, United States
Phelps, R., Department of Pathology, Mount Sinai School of Medicine, Box 1124, One Gustave L. Levy Place, New York, NY 10029, United States
Spiera, H., Department of Medicine, Mount Sinai School of Medicine, Box 1124, One Gustave L. Levy Place, New York, NY 10029, United States
Pines, M., Institute of Animal Science, Volcani Center, Bet Degan, Israel
Bona, C., Department of Microbiology, Mount Sinai School of Medicine, Box 1124, One Gustave L. Levy Place, New York, NY 10029, United States

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Abstract:

The endpoint of pathogenic events in scleroderma is fibrosis of the skin and internal organs. Fibrosis in scleroderma results from the over synthesis and deposition of collagen in the connective tissue. The morbidity and mortality of the scleroderm is very high and presently there is no specific treatment. Halofuginone is a drug with great potential for the treatment of scleroderma since it inhibits the synthesis of collagen type I by fibroblasts. We have studied the in vivo effect of halofuginone in tight skin (TSK) mice that spontaneously develop a scleroderma-like disease due to a genetic defect. Our results demonstrate that halofuginone prevented the occurrence of skin scleroris when administered to newborn mice and reduced cutaneous hyperplasia when administered in adult TSK mice. These effects correlated with a decreased number of cells synthesizing collagen gene transcripts and a reduction in the level of autoantibodies specific for human target antigens. These results indicate that halofuginone may have use as a therapeutic in the treatment of fibrotic disease.

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