everolimus + lonafarnib

Everolimus + lonafarnib is an investigational combination therapy being studied primarily for Hutchinson-Gilford Progeria Syndrome (HGPS) and progeroid laminopathies. Everolimus is a derivative of rapamycin and acts as an inhibitor of the mammalian target of rapamycin (mTOR), thereby reducing cell proliferation, DNA damage, and promoting autophagic clearance of toxic proteins such as progerin. Lonafarnib is a farnesyltransferase inhibitor that blocks the farnesylation process required for the production of progerin, the abnormal protein responsible for HGPS pathology. The combination targets two distinct disease pathways—lonafarnib reduces production of toxic progerin while everolimus enhances its clearance—potentially providing additive or synergistic benefits in improving vascular function and reducing disease burden in HGPS patients[1][2][4][5].