Combination of an hmg-coa reductase inhibitor and a farnesyl-pyrophosphatase synthase inhibitor for the treatment of diseases related to the persistence and/or accumulation of prenylated proteins

A method for the treatment of a skin disorder related to the accumulation of farnesylated and/or geranylgeranylated protein in skin cells, wherein the skin disorder is selected from the group consisting of natural skin aging, premature skin aging not related to a genetic mutation, and lipodystrophy, the method comprising the step of administering to an individual in need thereof an effective amount of at least one inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, and at least one aminobisphosphonate,

• wherein the HMG-CoA reductase inhibitor is selected from the group consisting of atorvastatin, simvastatin, pravastatin, rivastatin, mevastatin, fluindostatin, velostatin, fluvastatin, dalvastatin, cerivastatin, pentostatin, rosuvastatin, lovastatin, pitavastatin, and physiologically-acceptable salts thereof;
• wherein the aminobiphosphonate is selected from the group consisting of alendronic acid or the ionic form thereof, ibandronic acid or the ionic form thereof, neridronic acid or the ionic form thereof, olpadronic acid or the ionic form thereof, risedronic acid or the ionic form thereof, zoledronic acid or the ionic form thereof, icandronic acid or the ionic form thereof, minodronic acid or the ionic form thereof, 4-N,N-dimethylaminomethane diphosphonic acid or the ionic form thereof, and α-amino-(4-hydroxybenzylidene)diphosphonate;
• wherein the amount of the HMG-CoA reductase inhibitor and amount of aminobisphosphonate have a synergistic effect on reducing the accumulation of farnesylated and/or geranylgeranylated protein in skin cells;
• and
• wherein the HMG-CoA reductase inhibitor and aminobisphosphonate are formulated for administration on the skin.

A composition comprising a synergistically-effective amount of a combination of:

• at least one HMG-CoA reductase inhibitor selected from the group consisting of atorvastatin, simvastatin, pravastatin, rivastatin, mevastatin, fluindostatin, velostatin, fluvastatin, dalvastatin, cerivastatin, pentostatin, rosuvastatin, lovastatin, pitavastatin, and one of the physiologically-acceptable salts thereof;
• at least one aminobiphosphonate selected from the group consisting of alendronic acid or the ionic form thereof, ibandronic acid or the ionic form thereof, neridronic acid or the ionic form thereof, olpadronic acid or the ionic form thereof, risedronic acid or the ionic form thereof, zoledronic acid or the ionic form thereof, icandronic acid or the ionic form thereof, minodronic acid or the ionic form thereof, 4-N,N-dimethylaminomethane diphosphonic acid or the ionic form thereof, and α-amino-(4-hydroxybenzylidene)diphosphonate;
• said composition formulated for administration on the skin,
• wherein the amount of the HMG-CoA reductase inhibitor and amount of aminobisphosphonate have a synergistic effect on reducing the accumulation of farnesylated and/or geranylgeranylated protein in skin cells;
• and
• wherein the composition is administered for the treatment of a skin disorder related to the accumulation of farnesylated and/or geranylgeranylated protein in skin cells, selected from the group consisting of natural skin aging, premature skin ageing not related to a genetic mutation and lipodystrophy.