The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Nov. 23, 2010

Filed:

Jul. 25, 2007
Applicants:

Leslie B. Gordon, Foxboro, MA (US);

Francis S. Collins, Rockville, MD (US);

Thomas Glover, Ypsilanti, MI (US);

Michael W. Glynn, Darien, CT (US);

Brian C. Capell, Rumson, NJ (US);

Adrienne D. Cox, Chapel Hill, NC (US);

Channing J. Der, Chapel Hill, NC (US);

Inventors:

Leslie B. Gordon, Foxboro, MA (US);

Francis S. Collins, Rockville, MD (US);

Thomas Glover, Ypsilanti, MI (US);

Michael W. Glynn, Darien, CT (US);

Brian C. Capell, Rumson, NJ (US);

Adrienne D. Cox, Chapel Hill, NC (US);

Channing J. Der, Chapel Hill, NC (US);

Attorney:
Primary Examiner:
Assistant Examiner:
Int. Cl.
CPC ...
A61K 49/00 (2006.01); A61K 31/445 (2006.01); C12Q 1/48 (2006.01); A01N 43/42 (2006.01);
U.S. Cl.
CPC ...
Abstract

Although it can be farnesylated, the mutant lamin A protein expressed in Hutchison Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called 'progerin') that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.


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