Combination therapies for treatment of laminopathies, cellular aging, and atherosclerosis

Abstract

Provided herein are combination therapies for the treatment of progeroid diseases and conditions, cellular aging, bone diseases, and cardiovascular diseases. The provided combination therapies target the aberrant farnesylation of the mutant lamin A protein progerin and increase progerin clearance.

We claim: 
     
         1 . A method for treating a progeroid disease or condition, a cellular aging-related condition, a bone disease or condition, or a cardiovascular disease or condition, the method comprising:
 administering to a patient in need of such treatment a therapeutically effective amount of at least two active ingredients comprising:
 a farnesyltransferase inhibitor (FTI); and 
 an mTOR inhibitor. 
   
     
     
         2 . The method of  claim 1 , wherein the cellular aging related-condition is aberrant cellular senescence. 
     
     
         3 . The method of  claim 1 , wherein the cardiovascular disease is arteriosclerosis or atherosclerosis. 
     
     
         4 . The method of  claim 1 , wherein the FTI is lonafarnib. 
     
     
         5 . The method of  claim 1 , wherein the mTOR inhibitor is everolimus. 
     
     
         6 . The method of  claim 4 , wherein the lonafarnib is administered at a dosage between 115 mg/m 2  and 150 mg/m 2 . 
     
     
         7 . The method of  claim 1 , wherein the at least two active ingredients are administered simultaneously. 
     
     
         8 . The method of  claim 1 , wherein the at least two active ingredients are not administered simultaneously. 
     
     
         9 . A method for treating a progeroid disease or condition, a cellular aging-related condition, a bone disease or condition, or a cardiovascular disease or condition, the method comprising:
 administering to a patient in need of such treatment a therapeutically effective amount of at least two active ingredients consisting essentially of:
 a farnesyltransferase inhibitor (FTI); and 
 an mTOR inhibitor. 
   
     
     
         10 . The method of  claim 9 , wherein the cellular aging related-condition is aberrant cellular senescence. 
     
     
         11 . The method of  claim 9 , wherein the cardiovascular disease is arteriosclerosis or atherosclerosis. 
     
     
         12 . The method of  claim 9 , wherein the FTI is lonafarnib. 
     
     
         13 . The method of  claim 9 , wherein the mTOR inhibitor is everolimus. 
     
     
         14 . The method of  claim 12 , wherein the lonafarnib is administered at a dosage between 115 mg/m 2  and 150 mg/m 2 . 
     
     
         15 . The method of  claim 9 , wherein the at least two active ingredients are administered simultaneously. 
     
     
         16 . The method of  claim 9 , wherein the at least two active ingredients are not administered simultaneously.