Therapeutic applications of SMAD7
The invention provides methods and compositions for the treatment of inflammatory and/or tissue damage conditions. In particular, the use of Smad7 compositions delivered locally or systemically to a site of inflammation and/or tissue damage is described. Other specific embodiments concern treatment or prevention of side effects caused by radiation and/or chemotherapy, including but not limited to mucositis.
1. A method for treating oral mucositis or psoriasis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a protein comprising Smad7 (mothers against decapentaplegic homolog 7) fused to a protein transduction domain (PTD), wherein the protein translocates to the nucleus.
2. The method of claim 1 , wherein the protein comprising Smad7 is administered to the subject as a protein or is produced from an expression vector, wherein the expression vector expresses the protein within the subject.
3. The method of claim 1 , wherein the protein comprising Smad7 further comprises a regulatory domain that prevents Smad7 function in the absence of an activator, the method further comprising providing the activator.
4. The method of claim 1 , wherein the protein comprising Smad7 is administered in a formulation on a patch, in a gelatinous composition, in a microsphere, in a microbead or combination thereof.
5. The method of claim 1 , wherein the protein comprising Smad7 is administered locally to an affected region.
6. The method of claim 1 , wherein the protein comprising Smad7 is administered systemically.
7. The method of claim 1 , further comprising administering a second anti-inflammatory therapy to said subject.
8. The method of claim 1 , wherein the PTD is Tat.
9. The method of claim 1 , wherein the protein comprising Smad7 further comprises a detectable marker.
10. The method of claim 1 , wherein the subject has oral mucositis.
11. The method of claim 10 , further comprising administering a second mucositis therapy to said subject.
12. The method of claim 11 , wherein said second mucositis therapy is viscous 2% lidocaine, baking soda solution, saline solution, BAX solution, beta carotene, tocopherol, laser irradiation, silver-nitrate, misoprostol, leucovorin, systemic keratinocyte growth factor, pentoxifylline, allopurinol, systemic sucralfate, chlorhexidine gluconate or cryotherapy.
13. The method of claim 10 , wherein the subject comprises a subject having a transplant, a subject having cancer or a subject having a condition requiring radiation therapy.
14. The method of claim 13 , wherein the subject has cancer and the cancer is selected from the group consisting of oral cancer, colon cancer, breast cancer, head and neck cancer, pancreatic cancer and other cancers treated with upper body radiation or repeated cycles of chemotherapy.
15. The method of claim 10 , wherein the subject has undergone upper-body radiation.
16. The method of claim 1 , further comprising administering the protein comprising Smad7 to the subject a second time.
17. The method of claim 1 , wherein the subject has psoriasis.
18. The method of claim 1 , wherein the protein comprising Smad7 is formulated with one or more pharmaceutically acceptable excipients.
19. The method of claim 18 , wherein the one or more pharmaceutically acceptable excipients is selected for topical administration.
20. The method of claim 18 , wherein the one or more pharmaceutically acceptable excipients is selected for systemic administration.