Use of GLP-2 for the treatment or prevention, of bone-related disorders

• US 20070135345A1
• Filed: 11/22/2006
• Published: 06/14/2007
• Est. Priority Date: 09/18/2000
• Status: Abandoned Application

• Current Assignee: Sanos Bioscience A/S (C.C. Consulting A/S)
• Original Assignee: Sanos Bioscience A/S (C.C. Consulting A/S)
• Inventors: Henriksen, Dennis, Holst, Jens
• Application Number:
  US11/603,793
• Publication Number:
  US 20070135345A1
• Time in Patent Office: Days
• US Class Current: 514/5.800
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00

Abstract

The present invention relates to methods for prevention and treatment of bone-related or nutrition-related disorders using a GLP-2 molecule or GLP-2 activator either alone or in combination with another therapeutic. The invention also encompasses methods of monitoring the effectiveness of treatment of the invention.

Claims

1. A method for preventing a bone-related disorder, comprising administering to a patient in need thereof an effective amount of a material selected from the group consisting of GLP-2, GLP-2 analogues capable of binding and activating a GLP-2 receptor, agonists of the GLP-2 receptor, pharmaceutically acceptable derivatives of any of the foregoing and a mammalian expression vector comprising a nucleic acid encoding GLP-2 or an analogue thereof capable of binding and activating a GLP-2 receptor.

2. The method of claim 1 further comprising administering an effective amount of another therapeutic agent.

3. The method of claim 1, wherein said bone-related disorder is osteoporosis, hypercalcemia of malignancy, osteopenia due to bone metastases, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, Paget'"'"'s disease, osteodystrophy, myositis ossificans, Bechterew'"'"'s disease, malignant hypercalcemia, osteolytic lesions produced by bone metastasis, bone loss due to sex steroid hormone deficiency, bone abnormalities due to steroid hormone treatment, bone abnormalities caused by cancer therapeutics, osteomalacia, osteomalacia, hyperostosis, metastatic bone disease, immobilization-induced osteopenia, spinal cord injury, stroke, bariatric surgery, loss of bone mass associated with dietary restriction induced weight loss, or glucocorticoid-induced osteoporosis.

4. The method of claim 2, wherein said other therapeutic agent is an anti-osteoporosis agent.

5. The method of claim 4, wherein the anti-osteoporosis agent is parathyroid hormone, alendronate sodium, clodronate, etidronate, gallium nitrate, mithramycin, norethindrone acetate, pamidronate, or risedronate sodium.

6. The method of claim 2, wherein said other therapeutic agent is a steroid hormone.

7. The method of claim 6, wherein said steroid hormone is an estrogen, androgen, progestin, or glucocorticoid.

8. The method of claim 2, wherein said other therapeutic agent is a non-steroid hormone.

9. The method of claim 8, wherein said non-steroid hormone is calcitonin, calcitriol, growth hormone, melatonin, parathyroid hormone, ghrelin, leptin, PYY, NPY, GIP, excendin, prostaglandin, or thyroid hormone.

10. The method of claim 1, wherein the administering is performed via oral, intravenous infusion, subcutaneous injection, intramuscular injection, topical, depo injection, implantation, time-release mode, controlled-release mode, intracavitary, intranasal, inhalation, intratumor, intraocular intraperitoneal, intraorbital, intracapsular, intraspinal, intrasternal, intra-arterial, intradermal parenteral, transmucosal, nasal, rectal, intravaginal, sublingual, submucosal, transdermal, or transdermal patch route.

11. The method of claim 2, wherein said other therapeutic agent is administered before administering said material selected from the group consisting of GLP-2, GLP-2 analogues capable of binding and activating a GLP-2 receptor, agonists of the GLP-2 receptor, a pharmaceutically acceptable derivatives of any of the foregoing and a mammalian expression vector comprising a nucleic acid encoding GLP-2 or an analogue thereof capable of binding and activating a GLP-2 receptor.

12. The method of claim 2, wherein said other therapeutic agent is administered after administering said material selected from the group consisting of GLP-2, GLP-2 analogues capable of binding and activating a GLP-2 receptor, agonists of the GLP-2 receptor, a pharmaceutically acceptable derivatives of any of the foregoing and a mammalian expression vector comprising a nucleic acid encoding GLP-2 or an analogue thereof capable of binding and activating a GLP-2 receptor.

13. The method of claim 2, wherein said other therapeutic agent is administered concurrently with said material selected from the group consisting of GLP-2, GLP-2 analogues capable of binding and activating a GLP-2 receptor, agonists of the GLP-2 receptor, and pharmaceutically acceptable derivatives of any of the foregoing.

14. The method of claim 1, wherein said patient is not currently suffering from a bone resorption related disease but is at risk of developing such a disease.

15. The method of claim 1, further comprising measuring a biochemical marker for bone resorption before and/or after administration of said material selected from the group consisting of GLP-2, GLP-2 analogues capable of binding and activating a GLP-2 receptor, agonists of the GLP-2 receptor, a pharmaceutically acceptable derivatives of any of the foregoing and a mammalian expression vector comprising a nucleic acid encoding GLP-2 or an analogue thereof capable of binding and activating a GLP-2 receptor

18. The method of claim 1, wherein said material is a GLP-2 analogue with the amino acid sequence:

19. The method of claim 18 wherein said GLP-2 analogue sequence comprises

20. The method of claim 18 wherein said GLP-2 analogue sequence comprises

16. A method of determining the effectiveness of preventative or therapeutic treatment with a GLP-2 molecule or GLP-2 activator in a patient comprising:

(a) determining the level of one or more markers of bone resorption from a first patient tissue samples prior to said treatment and a second patient tissue sample after said treatment;

(b) comparing said levels of one or more markers in said tissue samples, wherein a decrease in said level in said second tissue sample indicates effective treatment.

17. The method of claim 16, wherein said marker is S-CTX and wherein the level of S-CTX is decreased.