Treating Learning Deficits with Inhibitors of HMG CoA Reductase

Abstract

The disclosure provides methods of treating cognitive disorders by administering a HMG CoA reductase inhibitor. Cognitive deficits treatable with the inhibitor compound include those associated with Angelman Syndrome, Neurofibromatosis-1, certain forms of X-linked mental retardation, tuberous sclerosis, Down Syndrome, autism, and attention deficit/hyperactivity disorder.

1 - 56 . (canceled) 
     
     
         57 . A method of treating a subject with a cognitive deficit, comprising:
 administering an effective amount of a hydroxymethylglutaryl CoA (HMG CoA) reductase inhibitor to a subject afflicted with a cognitive disorder associated with defects in the RAS-MAPK pathway.   
     
     
         58 . The method of  claim 57 , wherein the inhibitor comprises a statin. 
     
     
         59 . The method of  claim 58 , wherein the statin is selected from the group consisting of atorvastatin, cerivastatin, fluvastatin, lovostatin, pravastatin, pitavastatin, rovustatin, simvastatin, and compatible mixtures thereof. 
     
     
         60 . The method of  claim 57 , wherein the inhibitor comprises a mixture of HMG CoA reductase inhibitors. 
     
     
         61 . The method of  claim 57 , wherein the effective amount of the inhibitor is dose that does not significantly lower total serum cholesterol level in the subject. 
     
     
         62 . The method of  claim 57 , wherein the cognitive disorder is associated with dysregulation of small monomeric GTP binding protein activity. 
     
     
         63 . The method of  claim 62 , wherein the small monomeric GTP binding protein activity is that of RAS protein. 
     
     
         64 . The method of  claim 57 , wherein the cognitive disorder is associated with dysregulation of mitogen activated protein kinase (MAPK) signaling pathway. 
     
     
         65 . The method of  claim 57 , wherein the cognitive disorder is associated with increased inhibitory neuronal activity. 
     
     
         66 . The method of  claim 65 , wherein the inhibitory neuronal activity is associated with increased GABA-mediated inhibition. 
     
     
         67 . The method of  claim 66 , wherein the GABA-mediated inhibition is associated with activity of GABA A  or GABA B . 
     
     
         68 . The method of  claim 57 , further comprising administering a farnesyl transferase inhibitor, a geranylgeranyl transferase inhibitor, an inhibitor of γ-aminobutyric acid (GABA) mediated inhibition, or an inhibitor of GABA receptor activity. 
     
     
         69 . The method of  claim 68 , wherein the administering is adjunctive administration. 
     
     
         70 . The method of  claim 69 , wherein the adjunctive administration is simultaneous administration or sequential administration. 
     
     
         71 . The method of  claim 57 , wherein the subject has a normal cholesterol level.