Farnesyltransferase Inhibitors for Treatment of Laminopathies, Cellular Aging and Atherosclerosis
Description of Invention:
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, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 2003; 423(6937): 293-8), 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, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB, Gruenbaum Y, Khuon S, Mendez M, Varga R, Collins FS. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 2004; 8963-8968.).
Inventors:
Francis Collins (NHGRI) et al.
Patent Status:
DHHS Reference No. E-055-2005/0 --
U.S. Provisional Application No. 60/648,307 filed 28 Jan 2005
DHHS Reference No. E-055-2005/1 --
U.S. Provisional Application No. 60/707,192 filed 09 Aug 2005
Licensing Status: In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.
Portfolios: Internal Medicine Devices/Instrumentation
For Additional Information Please Contact: Fatima Sayyid M.H.P.M.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-4521
Email: sayyidf@mail.nih.gov
Fax: (301) 402-0220
