COMPOSITIONS AND METHODS FOR THE TREATMENT OR PREVENTION OF PULMONARY HYPERTENSION

1 . A method of treating or preventing pulmonary hypertension in a patient in need thereof, the method comprising:

administering a therapeutically effective amount of a compound that increases BMPR2 signaling (BMPR2 activator) to the patient with pulmonary hypertension, wherein the compound is an ascomycin, or a pharmaceutically acceptable salt, solvate, analog, or prodrug thereof.

2 . The method of claim 1 , wherein the compound is administered to improve exercise ability, delay clinical worsening, or combinations thereof.

3 . The method of claim 1 , wherein the pulmonary hypertension is associated with one or more of chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, an alveolar hypoventilation disorder, chronic exposure to high altitude, a developmental abnormality, thromboembolic obstruction of proximal and/or distal pulmonary arteries, a non-thrombotic pulmonary embolism, sarcoidosis, histiocytosis X, lymphangiomatosis or compression of pulmonary vessels.

4 . The method of claim 1 , wherein the pulmonary hypertension is pulmonary arterial hypertension (PAH).

5 . The method of claim 1 , wherein the patient experiences at least one of (a) adjustment of one or more hemodynamic parameters indicative of improvement of the pulmonary hypertension condition towards a more normal level versus baseline; (b) increase in exercise capacity versus baseline; (c) lowering of Borg dyspnea index (BDI) versus baseline; (d) improvement of one or more quality of life parameters versus baseline; (e) movement to a lower WHO functional class; and (f) a reduction in plasma natriuretic peptide levels versus baseline.

6 . The method of claim 1 , wherein the daily dose provides serum concentration of about 0.02 ng/mL to about 50 ng/mL.

7 . The method of claim 1 , wherein administration is oral, intra venus, or inhalation.

8 . The method of claim 1 , wherein the compound is ascomycin, desmethyl ascomycin (FK523), or prolyltacrolimus (FK525).

9 . A pharmaceutical composition comprising an ascomycin or a pharmaceutically acceptable salt, solvate, analog, or prodrug thereof, and at least one pharmaceutically acceptable excipient.