The invention provides methods for identifying protein modulators (e.g., antibody agonists) of eukaryotic cells. The methods typically involve expressing a combinatorial agent library (e.g., via lentiviral vectors) inside a eukaryotic cell type (e.g., a mammalian cell) and then directly selecting for agents (e.g., antibodies) that are agonist of a target molecule (e.g., a signaling receptor) that modulates a phenotype of or elicits a cellular response in the cell. Some related methods involve co-culturing a cell expressing a combinatorial agent library and a second cell, and then selecting agents that modulate a phenotype of or elicit a cellular response in the second cell. Preferably, the agents are antibodies and are introduced into and expressed in the starting cells under conditions each individual cell expresses no more than 3 different members of the antibody library. In addition, the invention provides methods for identifying protein agonists that capable of reprograming or trans-differentiating a target cell. Also provided in the invention are specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR or G-CSFR). Further provided in the invention are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

The present invention provides methods for treating anemia in a subject having kidney failure by administering a compound that inhibits hypoxia-inducible factor (HIF) prolyl hydroxylase.

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).

Methods for Identifying protein modulators of eukaryotic cells by expressing a combinatorial library of potential agonists inside a eukaryotic cell and then directly selecting for an agonist of a target molecule. Some methods involve co-culturing a cell expressing a combinatorial library of potential agonists and a second cell, and then selecting agents that modulate a phenotype of or a desired cellular response in the second cell. Preferably, the agonists are antibodies introduced into and expressed in the starting cells, such as agonist anti-EpoR, anti-TpoR, or G-CSFR antibodies. Also disclosed are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in stroke patients and in patients at risk for stroke. In particular, the invention relates to using assays that detect one or more biomarkers as diagnostic and prognostic biomarker assays in such patients.

The present invention provides methods for treating anemia in a subject having kidney failure by administering a compound that inhibits hypoxia-inducible factor (HIF) prolyl hydroxylase.

The invention is an ex vivo method for early detection of acute kidney injury in critical patients, which includes the measurements of fibroblast growth factor 23 (FGF23), klotho (KL) and erythropoietin (EPO) as biomarkers. These measurements are obtained from a venous blood sample or urine, and allow the determination of the following indicators: 1=([FGF23]p×[EPO]p); 2=([FGF23]p/[Klotho]p); 3=([EPO]p)/[Klotho]p); 4=([FGF23]p×[EPO]p)/[Klotho]p); where [X]p is defined as the plasma level of a specific molecule (X) which includes fibroblast growth factor 23 (FGF23), klotho (KL) or erythropoietin (EPO). If the value of the indicator 1, 2, 3, 4 or two or more thereof, is equal or higher than a cut-off point (10 U), the indicator and/or indicators allow the identification of patients with high risk of developing AKI, with a high sensitivity/specificity. Therefore high levels of the indicator are associated to a high probability of the presence/development of AKI, which allows to perform specific clinical interventions for patients with AKI. If the value of the indicator 1, 2, 3, 4 or two or more thereof, is lower than the previously mentioned cut-off point, the probability of presence/development of AKI is low, therefore patients require only standard treatment.

Disclosed herein are antibodies specific for erythroferrone and assays comprising the antibodies. Also disclosed are methods for using the assays for the diagnosis or monitoring of disease.

The present invention relates to use of pharmaceutical compositions that have as active ingredient the basic form of recombinant human erythropoietin (rhEPO) and that are administered nasally for the treatment of spinocerebellar ataxia (SCA) with mutations of CAG repeats type, particularly of SCA type 2. Another object of the present invention is a method for stratifying patients into responders and non-responders to treatment with the basic form of rhEPO.

Disclosed herein are antibodies specific for erythroferrone and assays comprising the antibodies. Also disclosed are methods for using the assays for the diagnosis or monitoring of disease.