Compositions and methods for the inhibition of fibrosis
Described herein is a mono-end PEGyated functional upstream domain (FUD), pharmaceutical compositions, and its use to inhibit fibrosis such as organ fibrosis, idiopathic pulmonary fibrosis and fibrosis associated with cancer. Also included are methods of probing for injured or repairing tissue in an individual in need thereof using the mono-end PEGyated-FUD.
1. A mono-end-PEGylated functional upstream domain (FUD), wherein the FUD peptide comprises SEQ ID NO: 1, and wherein the PEG is covalently linked to the N-terminus of FUD.
2. The mono-end-PEGylated FUD of claim 1 , wherein the PEG has a molecular weight of 10-40 kDa.
3. The mono-end-PEGylated FUD of claim 1 , further comprising a detectable label.
4. A pharmaceutical composition comprising the mono-end-PEGylated FUD of claim 1 and a pharmaceutically acceptable excipient.
5. The pharmaceutical composition of claim 4 in the form of a parenteral pharmaceutical composition.
6. The pharmaceutical composition of claim 4 , further comprising a second therapeutic agent that is an anti-fibrotic agent, an anti-cancer agent, or a combination thereof.
7. A method of inhibiting fibrosis in a subject in need thereof, comprising
administering to the subject a therapeutically effective amount of the mono-end-PEGylated FUD of claim 1 .
8. The method of claim 7 , wherein administration is subcutaneous administration.
9. The method of claim 7 , wherein the fibrosis comprises organ fibrosis.
10. The method of claim 9 , wherein the organ is liver, kidneys, and lungs.
11. The method of claim 10 , wherein the patient is suffering from chronic kidney disease.
12. The method of claim 11 , wherein the chronic kidney disease is associated with kidney transplant.
13. The method of claim 9 , wherein the patient is suffering from organ fibrosis associated with glomerulosclerosis, pulmonary fibrosis, peritoneum fibrosis, myocardial fibrosis, dermatofibrosis, post-surgery adhesions, benign prostatic hypertrophy, skeletal muscle fibrosis, dermatosclerosis, multiple sclerosis, pancreatic fibrosis, liver cirrhosis, myosarcoma, neurofibroma, diabetic nephropathy, Alzheimer's disease, or vascular fibrosis.
14. The method of claim 7 , wherein the patient is a human patient suffering from idiopathic pulmonary fibrosis.
15. The method of claim 7 , further comprising administering a second therapeutic anti-fibrotic agent for the treatment of organ fibrosis.
16. A method of inhibiting fibrosis associated with cancer metastasis, comprising administering to a subject in need thereof the mono-end-PEGylated FUD of claim 1 .
17. The method of claim 16 , wherein the cancer is ovarian, pancreatic or breast cancer.
18. The method of claim 16 , further comprising administering an anti-cancer agent.
19. A method of binding fibronectin associated with injured tissue or tissue to be repaired in an individual in need thereof, comprising administering to the individual a diagnostic amount of the mono-end-PEGylated FUD of claim 1 wherein the mono-end-pegylated FUD binds fibronectin.
20. The method of claim 19 , wherein the mono-end-PEGylated FUD comprises a detectable label.