Inhibitors of neuroligin 4-neurexin 1-beta protein-protein interaction for treatment of liver disorders

1. A method of treating, attenuating and/or preventing progression of a liver disorder, the method comprising administering a therapeutically effective amount of a recombinant soluble Nrx1b (rsNrxlb) comprising the extracellular domain of Nrx1b, capable of interfering with, inhibiting and/or preventing neuroligin 4 (NLGn4) Neurexin 113 (Nrx1b) protein-protein interaction; and a pharmaceutically acceptable carrier, thereby treating, attenuating and/or preventing the progression of the liver disorder.

2. The method of claim 1 , wherein the extracellular domain of Nrx1b consists of SEQ ID NO: 10.

3. The method of claim 1 , wherein the rsNrxlb consists of SEQ ID NO: 10.

4. The method of claim 1 , wherein the rsNrxlb competes with endogenous Nrx1b for binding to NLGn4.

5. The method of claim 1 , wherein the rsNrxlb is devoid of the intracellular domain and/or the transmembrane domain of Nrx1b.

6. The method of claim 1 , wherein the rsNrx1b is fused to Fc portion of an immunoglobulin molecule to form a fusion protein.

7. The method of claim 6 , wherein the fusion protein comprises the Fc portion of the immunoglobulin molecule fused to a peptide having an amino acid sequence as set forth in SEQ ID NO: 10.

8. The method of claim 1 , wherein NLGn4 is encoded by the sequence set forth in SEQ ID NO: 1.

9. The method of claim 1 , wherein Nrx1b is encoded by the sequence set forth in SEQ ID NO: 6.

10. The method of claim 1 , wherein the liver disorder comprises fibrosis.

11. The method of claim 1 , wherein the liver disorder is selected from the group consisting of: non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, hepatitis, liver adenoma, insulin hypersensitivity, liver cancer and any combination thereof.

12. The method of claim 11 , wherein the liver disorder is NAFLD.

13. The method of claim 11 , wherein the liver disorder is hepatocellular carcinoma.