THE GOVERNMENT OF THE UNITED STATES OF AMERICA ASREPRESENTED BY THE SECRETARY OF THE DEPARTMENT OFHEALTH AND HUMAN SERVICES;THE PROGERIA RESEARCH FOUNDATION, INC.;THE REGENTS OF THE UNIVERSITY OF MICH
发明人:
申请号：
EP06733984.6
公开号：
EP1853265B1
申请日:
2006.01.27
申请国别(地区):
EP
年份:
2016
代理人:
摘要：
Although it can he 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.
