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Anti-cancer drug prevents, reverses cardiovascular damage in mouse model of premature aging disorder
Date:10/6/2008

An experimental anti-cancer drug can prevent -- and even reverse -- potentially fatal cardiovascular damage in a mouse model of progeria, a rare genetic disorder that causes the most dramatic form of human premature aging, National Institutes of Health (NIH) researchers reported today.

In a study published in the Oct. 6 early online edition of the Proceedings of the National Academy of Sciences, a team led by Francis S. Collins, M.D., Ph.D., of the National Human Genome Research Institute (NHGRI), and Elizabeth G. Nabel, M.D., director of the National Heart, Lung and Blood Institute (NHLBI), describes its effort to use transgenic mice to identify and test potential therapies for children with Hutchinson-Gilford progeria syndrome.

There currently are no treatments for progeria, which is estimated to affect about one child in 4 million. At birth, children with progeria appear normal. But soon growth slows, and the children begin to show signs of accelerated aging, such as hair loss, wrinkled skin and loss of body fat. The most lethal damage, however, occurs within the children's major blood vessels. The children develop premature cardiovascular disease, which typically leads to death from heart attack or stroke at about the age of 13.

Building upon its past experiments in cells and mice, the NIH-led team examined the effects of an experimental cancer drug, tipifarnib, in a strain of mice genetically engineered to develop cardiovascular damage similar to that seen in progeria patients. Tipifarnib belongs to a class of drugs known as farnesyltransferase inhibitors (FTIs), which are being tested in people with myeloid leukemia, neurofibromatosis and other conditions. The team had previously found that FTI drugs could reverse structural abnormalities in skin cells taken from progeria patients and grown in the laboratory.

"This approach worked much better than we thought it would. Not only did this drug prevent these mi
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Contact: Geoff Spencer
spencerg@mail.nih.gov
301-402-0911
NIH/National Human Genome Research Institute
Source:Eurekalert

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