US2005158243A1PendingUtilityA1

Altering memory by affecting STAUFEN function

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Assignee: HELICON THERAPEUTICS INCPriority: Jun 25, 2002Filed: Dec 21, 2004Published: Jul 21, 2005
Est. expiryJun 25, 2022(expired)· nominal 20-yr term from priority
Inventors:Timothy P. TullyRoderick E. M. ScottRusiko Bourtchouladze
G01N 33/5088G01N 2500/00G01N 33/5023G01N 33/5008A61P 25/00G01N 33/5058G01N 33/6896G01N 33/502A61P 25/28G01N 33/5035
52
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Claims

Abstract

The present invention provides methods for screening a pharmaceutical agent for its ability to modulate long term memory formation, performance of a hippocampal-dependent cognitive task or STAUFEN function. The present invention also provides methods for modulating long term memory formation or performance of a hippocampal-dependent cognitive task by modulating staufen-dependent protein expression. The present invention further provides methods for treating a defect in long term memory formation associated with a defect in STAUFEN and methods for treating a defect in performance of a hippocampal-dependent cognitive task associated with a defect in STAUFEN.

Claims

exact text as granted — not AI-modified
1 . a method of screening for or identifying a pharmaceutical agent capable of modulating staufen function comprising the steps of: 
 a) introducing a pharmaceutical agent of interest into host cells expressing a STAUFEN::indicator fusion protein; and    b) determining STAUFEN function,    wherein a difference in the STAUFEN function determined in b) compared to the STAUFEN function of host cells of a) to which said pharmaceutical agent has not been administered identifies the pharmaceutical agent as one capable of modulating STAUFEN function.    
     
     
         2 . The method of  claim 1 , wherein STAUFEN function is determined by detecting and determining the level of STAUFEN::indicator fusion protein expression.  
     
     
         3 . The method of  claim 1 , wherein STAUFEN function is determined by detecting and determining the level of STAUFEN::indicator fusion protein mRNA produced.  
     
     
         4 . The method of  claim 1 , wherein STAUFEN function is determined by detecting and determining the level of STAUFEN::indicator fusion protein produced.  
     
     
         5 . The method of  claim 1 , wherein STAUFEN function is determined by detecting translocation of STAUFEN::indicator fusion protein into dendrites.  
     
     
         6 . The method of  claim 1 , wherein STAUFEN function is determined by measuring downstream gene products regulated by a staufen gene product.  
     
     
         7 . The method of  claim 1 , wherein STAUFEN function is determined by determining the distribution of neural granules in the cells.  
     
     
         8 . A method of screening a pharmaceutical agent for its ability to modulate long term memory formation in a mammal, comprising the steps of: 
 a) administering to a mammal a pharmaceutical agent of  claim 1  which modulates STAUFEN function;    b) training the mammal of step a) and a control mammal of the same species to which said pharmaceutical agent has not been administered under conditions sufficient to produce long term memory formation in said mammal;    c) assessing long term memory formation in the mammals trained in step b); and    d) comparing long term memory formation in the mammals assessed in step c),    wherein a difference in long term memory formation assessed in the mammal administered the pharmaceutical agent relative to long term memory formation assessed in the control mammal identified the pharmaceutical agent as one which capable of modulating long term memory formation in said mammal.    
     
     
         9 . The method of  claim 8 , wherein the animal is a rodent.  
     
     
         10 . A method of screening a pharmaceutical agent for its ability to modulate performance of a hippocampal-dependent cognitive task by a mammal, comprising the steps of: 
 a) administering to a mammal a pharmaceutical agent of  claim 1  which modulates STAUFEN function;    b) training the mammal of step a) and a control mammal of the same species to which said pharmaceutical agent has not been administered under conditions sufficient for performance of a specified hippocampal-dependent cognitive task by the mammal;    c) assessing performance of the hippocampal-dependent cognitive task by the mammals trained in step b); and    d) comparing performance of the mammals assessed in step c),    wherein a difference in performance of the specified hippocampal-dependent cognitive task by the mammal administered the pharmaceutical agent relative to performance of the cognitive task by the control mammal identifies the pharmaceutical agent as one which capable of modulating performance of the specified hippocampal-dependent cognitive task by the mammal.    
     
     
         11 . The method of  claim 10 , wherein the mammal is a rodent.  
     
     
         12 . A method of screening a pharmaceutical agent for its ability to modulate long term memory formation in a mammal, comprising the steps of: 
 a) administering a pharmaceutical agent of interest to a first mammal;    b) determining STAUFEN function in said mammal administered the pharmaceutical agent in step a) relative to STAUFEN function in a control mammal of the same species as said first mammal to which said pharmaceutical agent has not been administered;    c) selecting the pharmaceutical agent if STAUFEN function determined in step b) differs from the STAUFEN function in said control mammal;    d) administering the pharmaceutical agent selected in step c) to a second mammal;    e) training said second mammal administered the pharmaceutical agent in step d) and a control mammal of the same species as the second mammal to which said pharmaceutical agent has not been administered under conditions appropriate to produce long term memory formation in the mammals;    f) assessing long term memory formation in the mammals trained in step e); and    g) comparing long term memory formation in the mammals assessed in step f).    
     
     
         13 . The method of  claim 12 , wherein said mammal has a defect in long term memory formation associated with a defect in STAUFEN function.  
     
     
         14 . The method of  claim 12 , wherein said mammal is a rodent.  
     
     
         15 . A method of screening a pharmaceutical agent for its ability to modulate performance of a hippocampal-dependent cognitive task by a mammal, comprising the steps of: 
 a) administering a pharmaceutical agent of interest to a first mammal;    b) determining STAUFEN function in said mammal administered the pharmaceutical agent in step a) relative to STAUFEN function in a control mammal of the same species a as the first mammal to which said pharmaceutical agent has not been administered;    c) selecting said pharmaceutical agent if STAUFEN function determined in step b) differs from the STAUFEN function in said control mammal;    d) administering the pharmaceutical agent selected instep c) to a second mammal;    e) training said second mammal administered the pharmaceutical agent in step d) and a control mammal of the same species as the second mammal to which said pharmaceutical agent has not been administered under conditions appropriate for performance of a specified hippocampal-dependent cognitive task by the mammals;    f) assessing performance of said hippocampal-dependent cognitive task by the mammals trained in step e); and    g) comparing performance of said hippocampal-dependent cognitive task by the mammals assessed in step f).    
     
     
         16 . The method of  claim 15 , wherein said mammal is a rodent.  
     
     
         17 . A method of screening a pharmaceutical agent for its ability to modulate STAUFEN function in a mammal, comprising the steps of: 
 a) administering a pharmaceutical agent of interest to said mammal; and    b) determining STAUFEN function in said mammal administered said pharmaceutical agent in step a) relative to STAUFEN function in a control mammal of the same species to which said pharmaceutical agent has not been administered.    
     
     
         18 . The method of  claim 17 , wherein said mammal has a defect in long term memory formation associated with a defect in STAUFEN function.  
     
     
         19 . The method of  claim 17 , wherein said mammal is a rodent.  
     
     
         20 . A method of modulating long term memory formation in a mammal comprising modulating STAUFEN function in said animal.  
     
     
         21 . The method of  claim 20 , wherein long term memory formation is enhanced.  
     
     
         22 . The method of  claim 20 , wherein modulating STAUFEN function comprises administering to said mammal a pharmaceutical agent which modulates STAUFEN function in said mammal, in an amount effective to modulate STAUFEN function in said mammal.  
     
     
         23 . The method of  claim 20 , wherein said mammal is a rodent or a human.  
     
     
         24 . The method of  claim 20  comprising modulating STAUFEN protein expression in said mammal.  
     
     
         25 . The method of  claim 24 , wherein long term memory formation is enhanced.  
     
     
         26 . The method of  claim 24 , wherein modulating STAUFEN protein expression comprises administering to said mammal a pharmaceutical agent which modulates STAUFEN protein expression in said mammal, in an amount effective to modulate STAUFEN protein expression.  
     
     
         27 . The method of  claim 24 , wherein said mammal is a rodent or a human.  
     
     
         28 . A method of treating a mammal with a defect in long term memory formation associated with a defect in STAUFEN comprising increasing STAUFEN function in said mammal relative to STAUFEN function in said mammal prior to said treatment.  
     
     
         29 . The method of  claim 28 , wherein increasing STAUFEN function comprises administering to said mammal a pharmaceutical agent which is capable of increasing STAUFEN function in said mammal, in an amount effective to increase STAUFEN function relative to STAUFEN function in said mammal prior to administration of said pharmaceutical agent.  
     
     
         30 . The method of  claim 28 , wherein said mammal is a rodent or a human.  
     
     
         31 . The method of  claim 28  comprising increasing STAUFEN protein expression in said mammal relative to STAUFEN protein expression in said mammal prior to said treatment.  
     
     
         32 . The method of  claim 31 , wherein increasing STAUFEN protein expression comprises administering to said mammal a pharmaceutical agent which increases STAUFEN protein expression in said mammal, in an amount effective to increase STAUFEN protein expression relative to STAUFEN protein expression in said mammal prior to administration of said pharmaceutical agent.  
     
     
         33 . The method of  claim 31 , wherein said mammal is a rodent or a human.  
     
     
         34 . The method of  claim 28  comprising administering to said mammal an effective amount of STAUFEN, STAUFEN analog, biologically active STAUFEN fragment or STAUFEN fusion protein.  
     
     
         35 . The method of  claim 34 , wherein said mammal is a rodent or a human.  
     
     
         36 . The method of  claim 28  comprising administering to said mammal an effective amount of a nucleic acid sequence encoding STAUFEN, STAUFEN analog, biologically active STAUFEN fragment or STAUFEN fusion protein.  
     
     
         37 . The method of  claim 36 , wherein said mammal is a rodent or a human.  
     
     
         38 . The method of  claim 36 , wherein the nucleic acid sequence is incorporated into a viral vector.  
     
     
         39 . A method of modulating performance by a mammal of a hippocampal-dependent cognitive task comprising modulating STAUFEN function in said mammal.  
     
     
         40 . The method of  claim 39 , wherein performance by a mammal of a hippocampal-dependent cognitive task is enhanced.  
     
     
         41 . The method of  claim 39 , wherein modulating STAUFEN function comprises administering a pharmaceutical agent which modulates STAUFEN function in said mammal, in an amount effective to modulate STAUFEN function in said mammal.  
     
     
         42 . The method of  claim 39 , wherein said mammal is a rodent or a human.  
     
     
         43 . The method of  claim 39  comprising modulating STAUFEN protein expression.  
     
     
         44 . The method of  claim 43 , wherein performance by a mammal of a hippocampal-dependent cognitive task is enhanced.  
     
     
         45 . The method of  claim 43 , wherein modulating STAUFEN protein expression comprises administering a pharmaceutical agent which modulates STAUFEN protein expression in said mammal, in an amount effective to modulate STAUFEN protein expression in said mammal.  
     
     
         46 . The method of  claim 43 , wherein said mammal is a rodent or a human.  
     
     
         47 . A method of treating a mammal with a defect in performance of a hippocampal-dependent cognitive task, said defect in performance associated with a defect in STAUFEN, comprising increasing STAUFEN function in said mammal relative to STAUFEN function in said mammal prior to said treatment, thereby resulting in treatment of said mammal.  
     
     
         48 . The method of  claim 47 , wherein increasing STAUFEN function comprises administering to said mammal a pharmaceutical agent which increases STAUFEN function in said mammal, in an amount effective to increase STAUFEN function relative to STAUFEN function in said mammal prior to administration of said pharmaceutical agent.  
     
     
         49 . The method of  claim 47 , wherein said mammal is a rodent or a human.  
     
     
         50 . The method of  claim 47  comprising increasing STAUFEN protein expression in said mammal relative to STAUFEN protein expression in said mammal prior to said treatment.  
     
     
         51 . The method of  claim 50 , wherein increasing STAUFEN protein expression comprises administering to said mammal a pharmaceutical agent which increases STAUFEN protein expression in said mammal, in an amount effective to increase STAUFEN protein expression relative to STAUFEN protein expression in said mammal prior to administration of said pharmaceutical agent.  
     
     
         52 . The method of  claim 50 , wherein said mammal is a rodent or a human.  
     
     
         53 . The method of  claim 47  comprising administering to said mammal an effective amount of STAUFEN, STAUFEN analog, biologically active STAUFEN fragment or STAUFEN fusion protein.  
     
     
         54 . The method of  claim 53 , wherein said mammal is a rodent or a human.  
     
     
         55 . The method of  claim 47  comprising administering to said mammal an effective amount of a nucleic acid sequence encoding STAUFEN, STAUFEN analog, biologically active STAUFEN fragment or STAUFEN fusion protein.  
     
     
         56 . The method of  claim 55 , wherein said mammal is a rodent or a human.  
     
     
         57 . The method of  claim 55 , wherein the nucleic acid sequence is incorporated into a viral vector.

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