Available Technology

Farnesyltransferase Inhibitors for Treatment of Laminopathies, Cellular Aging and Atherosclerosis

Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare progressive childhood disorder characterized by premature aging (progeria). Recently, the gene responsible for HGPS was identified (Eriksson M, et al. Nature 2003), and HGPS joined a group of syndromes — the laminopathies — all of which are caused by various mutations in the lamin A/C gene (LMNA). Lamin A is one of the family of proteins that is modified post-translationally by the addition of a farnesyl group. In progeria, the abnormal protein (progerin) can still be farnesylated, however, a subsequent cleavage is blocked. The present invention describes a possible treatment of laminopathies, cellular aging and aging-related conditions such as HGPS through the use of farnesyltransferase inhibitors (FTIs) and other related compounds. This treatment should lead to a decrease in the accumulation of abnormal proteins such as progerin in case of HGPS patients and therefore reduce or eliminate many of the devastating clinical symptoms of the underlying biological defect of nuclear membrane instability (Goldman R, et al. PNAS 2004).
Patent Abstract: 
Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare progressive childhood disorder characterized by premature aging (progeria). Recently, the gene responsible for HGPS was identified (Eriksson M, et al. Nature 2003), and HGPS joined a group of syndromes — the laminopathies — all of which are caused by various mutations in the lamin A/C gene (LMNA). Lamin A is one of the family of proteins that is modified post-translationally by the addition of a farnesyl group. In progeria, the abnormal protein (progerin) can still be farnesylated, however, a subsequent cleavage is blocked. The present invention describes a possible treatment of laminopathies, cellular aging and aging-related conditions such as HGPS through the use of farnesyltransferase inhibitors (FTIs) and other related compounds. This treatment should lead to a decrease in the accumulation of abnormal proteins such as progerin in case of HGPS patients and therefore reduce or eliminate many of the devastating clinical symptoms of the underlying biological defect of nuclear membrane instability (Goldman R, et al. PNAS 2004). Francis Collins(NHGRI)➽ more inventions... U.S. Pat:7,838,531issued 2010-11-23 U.S. Pat:8,828,356issued 2014-09-09 U.S. Pat:8,691,501issued 2014-04-08 U.S. Pat:8,257,915issued 2012-09-04 US Application No. 12/905,838 US Application No. 14/336,457 Eriksson M, et al.PMID 12714972 Goldman RD, et al.PMID 15184648 Eggerton Campbell, Ph.D. Email:eggerton.campbell@nih.gov Phone: 301-402-1648 E-055-2005/2 Updated:Sep 24, 2015
Inventors: 
Francis Collins
Internal Laboratory Ref #: 
E-055-2005/2
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