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Originally published in Science Express on 16 February 2006
Science 17 March 2006:
Vol. 311. no. 5767, pp. 1621 - 1623
DOI: 10.1126/science.1124875
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Reports

A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse Model of Progeria

Loren G. Fong,1* David Frost,2 Margarita Meta,3 Xin Qiao,1 Shao H. Yang,1 Catherine Coffinier,1 Stephen G. Young1*

Progerias are rare genetic diseases characterized by premature aging. Several progeroid disorders are caused by mutations that lead to the accumulation of a lipid-modified (farnesylated) form of prelamin A, a protein that contributes to the structural scaffolding for the cell nucleus. In progeria, the accumulation of farnesyl–prelamin A disrupts this scaffolding, leading to misshapen nuclei. Previous studies have shown that farnesyltransferase inhibitors (FTIs) reverse this cellular abnormality. We tested the efficacy of an FTI (ABT-100) in Zmpste24-deficient mice, a mouse model of progeria. The FTI-treated mice exhibited improved body weight, grip strength, bone integrity, and percent survival at 20 weeks of age. These results suggest that FTIs may have beneficial effects in humans with progeria.

1 Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
2 Abbott Laboratories, Abbott Park, IL 60064, USA.
3 Department of Radiology, University of California, San Francisco, CA 94107, USA.

* To whom correspondence should be addressed. E-mail: lfong{at}mednet.ucla.edu; sgyoung{at}mednet.ucla.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)