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Peer-reviewed veterinary case report

A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria.

Journal:
Science (New York, N.Y.)
Year:
2006
Authors:
Fong, Loren G et al.
Affiliation:
Department of Medicine/Division of Cardiology · United States
Species:
rodent

Abstract

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.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/16484451/