Therapeutic use of bone morphogenetic proteins
The invention relates to a polypeptide selected from bone morphogenetic protein 10 (BMP10), or a bone morphogenetic protein 9 (BMP9) variant lacking osteogenic activity, for use in the treatment of a vascular disease or a respiratory disease. The invention also relates to novel BMP9 variants and to pharmaceutical compositions comprising said polypeptides.
1. A method of treating pulmonary arterial hypertension in a subject comprising administering to the subject a polypeptide which is a bone morphogenetic protein 9 (BMP9) variant having endothelial cell signaling activity and lacking osteogenic activity, wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of a substitution selected from the group consisting of F362A, D366A, I375A, L379A, 5402A, Y416A and Y418A.
2. The method of claim 1 , wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of the substitution F362A.
3. The method of claim 1 , wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of the substitution D366A.
4. The method of claim 1 , wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of the substitution I375A.
5. The method of claim 1 , wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of the substitution L379A.
6. The method of claim 1 , wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of the substitution 5402A.
7. The method of claim 1 , wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of the substitution Y416A.
8. The method of claim 1 , wherein the difference between the amino acid sequence of said BMP9 variant and the amino acid sequence of SEQ ID NO: 4 consists of the substitution Y418A.