Use of transforming growth factor-beta neutralizing antibodies and fusion proteins thereof in treating pain
View Patent ↗Provided herein are methods for treating pain and for reducing the excitability of nociceptors, comprising administering a TGF-β antagonist. In some embodiments, a TGF-β antagonist is a monoclonal TGF-β neutralizing antibody or a fusion product comprising a monoclonal TGF-β neutralizing antibody, a soluble receptor, an antisense oligodeoxynucleotides (ODNs), a ribozymes, a small inhibitory RNA (siRNA), Smad 6, Smad7, or a small molecule that blocks TGF-β signaling.
1. A method for treating pain, comprising administering to a subject in need thereof a composition comprising a TGF-β antagonist in a therapeutically effective amount to treat pain, wherein said TGF-β antagonist is selected from the group consisting of TGF-β-neutralizing antibodies and fusion proteins thereof.
2. A method for reducing sensation of pain in a subject experiencing pain, comprising administering to said subject a composition comprising a TGF-β antagonist, wherein said TGF-β antagonist is selected from the group consisting of TGF-β-neutralizing antibodies and fusions proteins thereof, and whereby said TGF-beta antagonist is administered in an amount therapeutically effective to reduce excitability of said subject's nociceptors that have become hyperexcited upon activation by TGF-beta and, thereby, to reduce sensation of said pain.
3. The method of any of claim 1 , or 2 , wherein said TGF-β antagonist is a monoclonal TGF-β-neutralizing antibody.
4. The method of any of claim 1 , or 2 , wherein said TGF-β antagonist is a fusion protein comprising a monoclonal TGF-β-neutralizing antibody and an antibody against transient receptor potential Vanilloid receptor 1.
5. The method of any of claim 1 , or 2 , wherein said TGF-β antagonist is a fusion protein comprising a monoclonal TGF-β-neutralizing antibody and an antibody against TrkA.
6. The method of any of claim 1 , or 2 , wherein said TGF-β antagonist is a fusion protein comprising a monoclonal TGF-β-neutralizing antibody and an antibody against NGF.
7. The method of any of claim 1 , or 2 , wherein said TGF-β antagonist is an engineered TGF-β-neutralizing antibody selected from the group consisting of chimeric antibodies, de-immunized antibodies, humanized antibodies, Fab or scFv antibody fragments, multimeric scFvs, and fully human antibodies.
8. The method of any of claim 1 , or 2 , wherein said TGF-β antagonist is a TGF-β1 antagonist.
9. The method of any of claim 1 , or 2 , wherein said pain is pain in inflammatory disease.
10. The method of claim 9 , wherein said inflammatory disease is a member selected from the group consisting of rheumatoid arthritis, diabetic neuropathy, intestinal inflammation of ulcerative colitis or Crohn's disease, radiation-induced fibrosis, pancreatitis, and myocarditis.
11. The method according to claim 10 , wherein said inflammatory disease is rheumatoid arthritis.
12. The method according to claim 10 , wherein said inflammatory disease is diabetic neuropathy.
13. The method according to claim 10 , wherein said inflammatory disease is intestinal inflammation of ulcerative colitis or Crohn's disease.
14. The method according to claim 10 , wherein said inflammatory disease is radiation-induced fibrosis.
15. The method according to claim 10 , wherein said inflammatory disease is pancreatitis.
16. The method according to claim 10 , wherein said inflammatory disease is myocarditis.
17. The method of any of claim 1 , or 2 , wherein said pain is pain in cancer.
18. The method of any of claim 1 , or 2 , wherein said administration is local administration.