USE OF H3K9me3 MODULATION FOR ENHANCING COGNITIVE FUNCTION

Abstract

Use of H3K9me3 modulation for enhancing cognitive function and treating anxiety related disorders is presented. A composition is administered to the subject comprising a therapeutically effective amount of a SUV39H1 inhibitor comprising analogs of ETP69. The therapeutically effective amount is effective in treating cognitive dysfunction in aging and age-related disorders.

1 . A method of prevention or alleviation of a cognitive dysfunction in a subject in need thereof, the method comprising administering a therapeutically effective amount of an SUV39H1 inhibitor compound having the structure of Formula (I): 
       
         
           
           
               
               
           
         
       
       wherein, p is 2, 3 or 4; and
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 16 , and R 18  are independently hydrogen, halogen, —N 3 , —CF 3 , —CCl 3 , —CBr 3 , —Cl 3 , —CN, —CHO, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 2 , —SO 2 Cl, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl. 
 
     
     
         2 . The method of  claim 1 , wherein the SUV39H1 inhibitor compound is Rac-(3S,6S,7S,8aS)-6-(benzo[d][1,3]dioxol-5-yl)-2,3,7-trimethyl-1,4-dioxohexahydro-6H-3,8a-epidithiopyrrolo[1,2-a]pyrazine-7-carbonitrile) (ETP69). 
     
     
         3 . The method of  claim 1 , wherein the SUVH31 inhibitor compound is administered together with a cognitive enhancer. 
     
     
         4 . The method of  claim 3 , wherein the cognitive enhancer is a cholinesterase inhibitor selected from a group comprising tacrine, donepezil, rivastigmine, and galantamine, or a combination thereof. 
     
     
         5 . The method of  claim 2 , wherein the cognitive enhancer is an NMDA agonist or an NMDA antagonist. 
     
     
         6 . The method of  claim 3 , wherein the cognitive enhancer is an ampakine. 
     
     
         7 . The method of  claim 3 , wherein the cognitive enhancer is a BZD/GABA receptor complex modulator. 
     
     
         8 . The method of  claim 3 , wherein the cognitive enhancer is a serotonin antagonist. 
     
     
         9 . The method of  claim 3 , wherein the cognitive enhancer is a nicotinic class compound. 
     
     
         10 . The method of  claim 3 , wherein the cognitive enhancer is a muscarinic class compound. 
     
     
         11 . The method of  claim 3 , wherein the cognitive enhancer is a PDE inhibitor. 
     
     
         12 . The method of  claim 3 , wherein the cognitive enhancer is a G protein class compound. 
     
     
         13 . The method of  claim 3 , wherein the cognitive enhancer is a channel modulator. 
     
     
         14 . The method of  claim 3 , wherein the cognitive enhancer is an immunotherapeutic class compound. 
     
     
         15 . The method of  claim 3 , wherein the cognitive enhancer is an anti-amyloid or amyloid lowering agent. 
     
     
         16 . The method of  claim 3 , wherein the cognitive enhancer is a statin or a PPARS modulator 
     
     
         17 . The method of  claim 1 , wherein the SUVH31 inhibitor compound is administered together with a lifestyle cognitive enhancer. 
     
     
         18 . The method of  claim 17 , wherein the lifestyle cognitive enhancer is mental or physical exercise. 
     
     
         19 . The method of  claim 17 , wherein the lifestyle cognitive enhancer is a dietary supplement. 
     
     
         20 . The method of  claim 19 , wherein the dietary supplement is an antioxidant, a mitochondrial function enhancer, caffeine, omega-3 or Docosahexaenoic acid (DHA).