Methods for treating pulmonary disease with a ligand binding domain of a TGF-β type II receptor
In some aspects, the invention teaches pharmaceutical compositions that include a TGF-β ligand trap, and methods of using a TGF-β ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-β ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-β signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-β ligand trap to reduce right ventricular systolic pressure in a subject.
1 . A method of treating, preventing, or reducing the progression rate of pulmonary fibrosis associated with excessive growth differentiation factor 15 (GDF15) signaling in a subject, the method comprising: administering a therapeutically effective amount of a transforming growth factor-β (TGF-β) ligand trap to the subject, wherein the TGF-β ligand trap comprises a sequence that is at least 95% identical to the sequence as set forth in SEQ ID NO: 1, and wherein the TGF-β ligand trap binds GDF15, TGF-β1, and/or TGF-β3.
2 . The method of claim 1 , wherein the TGF-β ligand trap comprises a sequence that is at least 99% identical to the sequence as set forth in SEQ ID NO: 1, and wherein the TGF-β ligand trap binds GDF15, TGF-β1, and/or TGF-β3.
3 . The method of claim 1 , wherein the TGF-β ligand trap comprises a sequence that is 100% identical to the sequence as set forth in SEQ ID NO: 1, and wherein the TGF-β ligand trap binds GDF15, TGF-β1, and/or TGF-β3.
4 . The method of claim 1 , wherein the TGF-β ligand trap is formulated for oral, via inhalation, nasal, sublingual, buccal, subcutaneous, intradermal, intramuscular, intravenous, intraperitoneal, or parenteral administration; and/or wherein the TGF-β ligand trap is formulated for modified release, sustained release, or controlled release, or a combination thereof.
5 . The method of claim 1 , wherein the amount of TGF-β ligand trap administered to the subject is 0.1-10 mg/kg of body weight.
6 . The method of claim 1 , wherein the TGF-β ligand trap is administered to the subject 1-7 times per month; and/or wherein the TGF-β ligand trap is administered to the subject for 1-5 days, 1-5 weeks, 1-5 months, or 1-5 years.
7 . The method of claim 1 , wherein the subject is a human.
8 . A method of treating, preventing, or reducing the progression rate of pulmonary fibrosis associated with excessive plasminogen activator inhibitor-1 (PAI-1) signaling in a subject, the method comprising: administering a therapeutically effective amount of a TGF-β ligand trap to the subject, wherein the TGF-β ligand trap comprises a sequence that is at least 95% identical to the sequence as set forth in SEQ ID NO: 1, and wherein the TGF-β ligand trap binds GDF15, TGF-β1, and/or TGF-β3-.
9 . The method of claim 8 , wherein the TGF-β ligand trap comprises a sequence that is at least 99% identical to the sequence as set forth in SEQ ID NO: 1, and wherein the TGF-β ligand trap binds GDF15, TGF-β1, and/or TGF-β3.
10 . The method of claim 8 , wherein the TGF-β ligand trap comprises a sequence that is 100% identical to the sequence as set forth in SEQ ID NO: 1, and wherein the TGF-β ligand trap binds GDF15, TGF-β1 and/or TGF-β3.
11 . The method of claim 8 , wherein the TGF-ligand trap is formulated for oral, via inhalation, nasal, sublingual, buccal, subcutaneous, intradermal, intramuscular, intravenous, intraperitoneal, or parenteral administration; and/or wherein the TGF-β ligand trap is formulated for modified release, sustained release, or controlled release, or a combination thereof.
12 . The method of claim 8 , wherein the amount of TGF-β ligand trap administered to the subject is 0.1-10 mg/kg of body weight.
13 . The method of claim 8 , wherein the TGF-β ligand trap is administered to the subject 1-7 times per month; and/or wherein the TGF-β ligand trap is administered to the subject for 1-5 days, 1-5 weeks, 1-5 months, or 1-5 years.
14 . The method of claim 8 , wherein the subject is a human.