Methods for the prevention and treatment of enthesopathy and related disorders
The present invention shows that TGF-β is activated in tendon-bone insertion in both a semi-Achilles tendon transection (SMTS) mouse model and a dorsiflexion immobilization (DI) mouse model of enthesopathy. High concentrations of active TGF-β recruited mesenchymal stromal/stem cells (MSCs) and led to excessive vessel formation, bone deterioration and fibrocartilage calcification. The invention provides uses and methods for prophylaxis and treatment of enthesopathies by inhibition of TGF-β.
1. A method for the treatment of enthesophytes in the Posterior Calcaneal Tuberosity (PCT) and/or enthesis degeneration of the Achilles tendon of a subject in need thereof comprising administering to the subject an effective amount of a transforming growth factor-β (TGF-β) inhibitor.
2. The method of claim 1 , wherein the transforming growth factor-β (TGF-β) inhibitor is an antibody which binds TGF-β with high affinity.
3. The method of claim 2 , wherein the antibody is selected from the group consisting of 1D11, fresolimumab, and galunisertib.
4. The method of claim 3 , wherein the antibody is 1D11.
5. The method of claim 1 , wherein the transforming growth factor-β (TGF-β) inhibitor is a biologically active agent which inhibits expression of TGF-β in the cells of the subject.
6. The method of claim 1 , wherein the transforming growth factor-β (TGF-β) inhibitor is a biologically active agent which is an antagonist to the TGF-β receptor.
7. The method of claim 1 , wherein the TGF-β inhibitor is administered with a pharmaceutically acceptable carrier.
8. The method of claim 1 , wherein the TGF-β inhibitor is administered systemically.
9. The method of claim 1 , wherein the TGF-β inhibitor is administered locally at the site of an injury or enthesis of the subject.
10. The method of claim 1 , wherein the TGF-β inhibitor is administered at a dose of between 0.1 mg/kg to 100 mg/kg.
11. The method of claim 1 , wherein the TGF-β inhibitor is administered with at least one additional biologically active agent.
12. The method of claim 11 , wherein the at least one biologically active agent is in the class of angiotensin II type 1 receptor (AT 1 ) antagonists.
13. The method of claim 12 , wherein the AT 1 antagonist is losartan.