Novel therapeutic and diagnostic products and methods

Abstract

The present invention relates to the use of p11 as a drug target as well as a tool for the diagnosis, treatment and development of p11/5-HT receptor related disorders. The invention further relates to p11 knock-out animals as well as p11 transgenic animals and their use as models for the development of novel psychotherapeutic agents, and to methods of diagnosis, prophylaxis and treatment of p11/5-HT receptor related disorders.

1 - 39 . (canceled) 
     
     
         40 . A method to identify p11 modulators useful to treat or ameliorate p11/5-HT receptor related disorders, wherein the method comprises:
 providing a first sample and a second sample, e.g., a cell culture or cell or tissue sample, containing equivalent amounts of p11 gene product (e.g., protein or mRNA); contacting the first sample with the candidate p11 modulator; and determining whether the amounts of p11 gene product in the first sample has changed, wherein an increased amount of gene product indicate that the candidate modulators can be useful to treat or ameliorate disorders associated with abnormally low level of p11 while a decreased amount indicates that the candidate modulators can be useful to treat or ameliorate disorders associated with abnormally low level of p11; or   providing a first sample and a second sample containing equivalent number of 5-HT 1B  and/or 5-HT 4  receptors at cell surface; contacting the first sample with the candidate p11 modulator; and determining whether the number of 5-HT 1B  and/or 5-HT 4  receptors at cell surface of the first sample has changed relative to the second sample, wherein an increased number of 5-HT 1B  and/or 5-HT 4  receptors at cell surface indicate that the candidate modulators can be useful to treat or ameliorate disorders associated with abnormally low level of p11 while a decreased number of 5-HT 1B  and/or 5-HT 4  receptors at cell surface indicates that the candidate modulators can be useful to treat or ameliorate disorders associated with abnormally low level of p11; or   contacting a candidate p11 modulator with a cell comprising a reporter gene operably linked to a p11 promoter, and using the reporter gene expression level as a proxy for p11 expression; or   assaying for the ability of a candidate modulator to up-regulate p11 expression or increase p11 activities associated with 5-HT 1B  and/or 5-HT 4  so as to recruit 5-HT 1B  and/or 5-HT 4  receptors at the neuronal plasma membrane; or   assaying for the ability of a candidate modulator to down-regulate p11 expression or inhibit or reduce p11 activities associated with 5-HT 1B  and/or 5-HT 4  so as to reduce or inhibit p11's ability to recruit 5-HT 1B  and/or 5-HT 4  receptors to neuronal plasma membrane.   
     
     
         41 . The method according to  claim 40 , wherein the disorders associated with abnormally low levels of p11 are selected from depression, obsessive compulsive disorder, drug addiction, eating disorders, attention deficit disorder or attention deficit hyperactive disorder, and Alzheimer's disease. 
     
     
         42 . The method according to  claim 40 , wherein the disorders associated with high levels of p11 include, but are not limited to mania, dipolar disorder, anxiety disorders, aggression, sleep disorders, sexual dysfunction and gastrointestinal disorders. 
     
     
         43 . A method to identify p11 mimetics useful to treat or ameliorate disorders associated with abnormally low level of p11 according to  claim 40 , wherein the method comprises assaying for the ability of a candidate p11 mimetic to associate or interact with 5-HT 1B  and/or 5-HT 4  receptors so as to recruit 5-HT 1B  and/or 5-HT 4  receptors to the neuronal plasma membrane. 
     
     
         44 . A method according to  claim 43 , wherein the disorder is depression. 
     
     
         45 . The method according to  claim 40 , wherein the p11/5-HT receptor related disorder is a p11/5-HT 1B  receptor related disorder. 
     
     
         46 . The method according to  claim 40 , wherein the p11/5-HT receptor related disorder is a p11/5-HT 4  receptor related disorder. 
     
     
         47 . A cell comprising a reporter gene operably linked to a p11 promoter. 
     
     
         48 . A method of studying p11/5-HT receptor related disorders or to develop novel psychotherapeutic agents useful for the treatment of p11/5-HT receptor related disorders comprising: a) administering an effective amount of said psychotropic agent to p11 knock-out mice and control mice; b) assessing the levels of p11 level and/or behavioral responses to said agent in said p11 knock-out mice and control mice; c) comparing said p11 level and/or behavioral responses in p11 knock-out mice with control mice.