Novel tissue protective erythropoietin receptor (nepor) and methods of use

Abstract

There is disclosed a molecular composition(s) of a novel tissue protective erythropoietin (EPO) binding receptor protein complex, termed NEPOR. Presence of NEPOR components on a tumour allows EPO to impinge on the survival of associated cells thereby enhancing tumour progression and negatively effecting patient survival. Presence of NEPOR represents a prognostic biomarker for poorer patient outcome. Thus, methods are provided for stratifying patients having a tumour as suitable (i.e. NEPOR not present) or non-suitable (i.e., NEPOR present) for EPO treatment, comprising: (a) isolating a tissue sample from an individual who is receiving or is a candidate for receiving erythropoietin, (b) determining the level of expression of the NEPOR gene(s) (mRNA) and/or the presence of the NEPOR gene product (protein) from the isolated tissue, and (c) correlating the presence of an NEPOR gene expression product or the presence of NEPOR protein to a physiological response to the treatment with erythropoietin. Furthermore, by disclosing the molecular compositions of NEPOR species, there are disclosed methods for rationally identifying/designing NEPOR modulating therapeutics. Methods also are provided for treating neurological insults such as stroke (via enhancement of NEPOR activity) and cancer (via down-regulation of cyto-protective signaling from NEPOR).

1 .- 17 . (canceled) 
     
     
         18 . A method of enhancing the effectiveness of EPO therapy in a patient, comprising administering to said patient, in conjunction with EPO therapy, an siRNA specific for EPH-B4. 
     
     
         19 . The method of  claim 18 , wherein the siRNA is selected from the group of nucleic acid duplexes consisting of SEQ ID NO: 242 and SEQ ID NO: 243; SEQ ID NO: 244 and SEQ ID NO: 245; SEQ ID NO: 246 and SEQ ID NO: 247; SEQ ID NO: 248 and SEQ ID NO: 249; SEQ ID NO: 250 and SEQ ID NO: 251; SEQ ID NO: 252 and SEQ ID NO: 253; SEQ ID NO: 254 and SEQ ID NO: 255; SEQ ID NO: 256 and SEQ ID NO: 257; SEQ ID NO: 258 and SEQ ID NO: 259; and SEQ ID NO: 260 and SEQ ID NO: 261. 
     
     
         20 . The method of  claim 18 , wherein the siRNA is a duplex of SEQ ID NO: 266 and SEQ ID NO: 267. 
     
     
         21 . The method of  claim 18 , wherein the siRNA is a duplex of SEQ ID NO: 219 and SEQ ID NO: 220.