Abstract: A novel monoclonal antibody and like antigen-binding molecules against transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFE2) are provided with unique immunological and biological properties useful in the therapy of affective disorders such as depression and bipolar disorders as well as anxiety disorders. In addition, pharmaceutical compositions and kits comprising such antibody and derivatives thereof are described.

Abstract: The present invention relates to a method for identifying a TMEFF2 modulator, comprising (a) contacting a cell which expresses TMEFF2 with a candidate compound to be tested; (b) measuring whether said compound to be tested decreases or increases the level of a constituent of the cAMP signalling pathway, preferably the CRH signalling pathway, in said cell when compared to a corresponding cell which does not express TMEFF2; (b?) optionally determining whether said compound is capable of reduncing the binding between Activin and TMEFF2; and (c) identifying said modulator compound. Furthermore, a method for identifying a TMEFF2 modulator comprising determining whether said TMEFF2 modulator is capable of reducing the binding between Activin and TMEFF2 is contemplated. It also relates to uses and methods applying a TMEFF2 agonist for the treatment of Cushing's Syndromes and a TMEFF2 modulator for the treatment of affective disorders.