METHOD TO IDENTIFY MODULATORS OF B-RAF PROTEIN KINASE AND THEIR USE FOR THE TREATMENT OF ANXIETY AND DEPRESSION

摘要

The present invention relates to a method for identifying a compound capable of modulating an anxiety or depression disorder comprising the steps of: (a) contacting a composition comprising a B-Raf protein or a B-Raf gene in expressible form or a transcript thereof with a compound under conditions that allow for an interaction of the B-Raf protein or the B-Raf gene or a transcript thereof and the compound; and (b) measuring whether said interaction, if any, results in (i) a change of B-Raf kinase activity compared to B-Raf kinase activity in the absence of said compound; (ii) a modulation of the expression of the B-Raf gene compared to B-Raf gene expression in the absence of said compound; or (iii) the formation of a complex between the compound and the B-Raf protein, wherein such a change in activity, modulation of expression or the formation of a complex is indicative of the compound being a modulator of an anxiety or depression disorder. Further, the invention relates to a method for treating an anxiety or depression disorder in an individual comprising administering to the individual an effective amount of a compound inhibiting B-Raf kinase activity or gene expression and to a use of a compound that inhibits B-Raf kinase activity or gene expression in the manufacture of a pharmaceutical composition for treating an anxiety or depression disorder. Moreover, the invention relates to a method of diagnosing a B-Raf associated anxiety or depression disorder and to a genetically engineered mouse. Finally, the invention also relates to a method of identifying another gene contributing to the pathophysiology of an anxiety or depression disorder apart from B-Raf.