Use of GLP-2 and related compounds for the treatment, prevention, diagnosis, and prognosis of bone-related disorders and calcium homeostasis related syndromes
The present invention relates to methods for prevention and treatment of bone-related disorders and calcium homeostasis related syndromes using a GLP-2 molecule or GLP-2 activator either alone or in combination with another therapeutic. The present invention also encompasses methods of diagnosing or monitoring the progression of a disorder. The invention also encompasses methods of monitoring the effectiveness of treatment of the invention.
1. A therapeutic composition comprising
a) a first active component which promotes bone formation and promotes bone resorption; and
b) a second active component which is a GLP-2, or an analogue or derivative or mimic of GLP-2 having the ability to bind and activate a GLP-2 receptor, or is a GLP-2 receptor agonist.
2. A composition as claimed in claim 1 , comprising as component (a) a PTH receptor binding ligand.
3. A composition as claimed in claim 2 , wherein the PTH receptor binding ligand is a PTH, an active fragment of PTH, PTHrP, an active fragment of PTHrP, or is an analogue or derivative of any one of said ligands having the ability to bind and activate a PTH receptor.
4. A composition as claimed in claim 2 , wherein component (a) is a PTH-1 receptor binding ligand.
5. A composition as claimed in claim 2 , wherein said component (a) is also a PTH -2 receptor activating ligand.
6. A composition as claimed in claim 2 , wherein said component (a) is not an activator for the PTH-2 receptor.
7. A composition as claimed in claim 2 , wherein component (a) is a full length PTH or is a C-terminal truncated PTH, optionally modified from a natural sequence by substitution of one or more amino acids.
8. A composition as claimed in claim 7 , wherein component (a) is a full length PTH or an N-terminal fragment containing at least the first 31 amino acid residues of PTH, optionally modified from a natural sequence by substitution of one or more amino acids.
9. A composition as claimed in claim 8 , wherein component (a) is [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1-31)NH(2).
10. A composition as claimed in claim 7 , wherein said component (a) is hPTH (1-84), hPTH (1-37), hPTH (1-36), hPTH (1-34), hPTH (1-31), or a cyclic derivative of any of the foregoing.
11. A composition as claimed in claim 2 , wherein said component (a) is a PTH (1-9) fragment, optionally containing substitutions of natural or unnatural amino acids whilst maintaining PTH1 receptor signal activation activity and conjugated to an effective PTH1 receptor binding moiety.
12. A composition as claimed in claim 2 , wherein said component (a) is full length PTHrP or is a C-terminal truncated PTHrP, optionally modified from a natural sequence by substitution of one or more amino acids.
13. A composition as claimed in claim 12 , wherein said component (a) is a PTHrP (1-40), optionally modified from a natural sequence by substitution of one or more amino acids.
14. A composition as claimed in claim 1 , wherein said component (b) is GLP-2 (1-34).
15. A composition as claimed in claim 8 , wherein said component (b) is GLP-2 (1-34).
16. A composition as claimed in claim 1 , wherein said composition is formulated for administration by injection.