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

2006; American Association for the Advancement of Science; Volume: 311; Issue: 5767 Linguagem: Inglês

10.1126/science.1124875

1095-9203

Loren G. Fong, David J. Frost, Margarita Meta, Xin Qiao, Shao H. Yang, Catherine Coffinier, Stephen G. Young,

Genomics and Chromatin Dynamics

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.