Methods of activating a melanocortin-4 receptor pathway in obese subjects

• US 8,476,227 B2
• Filed: 12/29/2010
• Issued: 07/02/2013
• Est. Priority Date: 01/22/2010
• Status: Active Grant

• Current Assignee: Ethicon Endo-Surgery, Inc. (Johnson & Johnson), The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Ethicon Endo-Surgery, Inc. (Johnson & Johnson), The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Kaplan, Lee M., Stylopoulos, Nicholas, Harris, Jason L.
• Primary Examiner(s): LANDSMAN, ROBERT S
• Application Number:
  US12/980,635
• Publication Number:
  US 20110263490A1
• Time in Patent Office: 916 Days
• Field of Search: None
• US Class Current: 514/4.8
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: G01N 2333/726 G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
• CPC Class Codes: G01N 2800/04 Endocrine or metabolic disorders
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

Methods and therapeutics are provided for treating metabolic disorders by activation of melanocortin signaling pathways. Generally, the methods and therapeutics can induce activation of melanocortin receptor signaling to increase energy expenditure and induce weight loss. In one embodiment, a method for performing a diagnostic procedure can be chosen, energy expenditure then assess in light of the diagnostic procedure and a definitive procedure(s) can be selected dependent on the outcome of the energy assessment. In another embodiment, a diagnostic procedure can be chosen to activate melanocortin receptor pathways, energy expenditure can be assessed and a definitive procedure(s) can be chosen that selectively and optimally activate melanocortin receptor pathways.

Claims

1. A method of activating a melanocortin-4 receptor (MC4R) pathway in an obese subject, the method comprising:

(a) performing a first intervention on a subject, wherein the first intervention is a non-surgical procedure;

(b) measuring energy expenditure of the subject to measure MC4R pathway activation in response to the first intervention; and

(c) performing a second intervention that activates the melanocortin receptor pathway, wherein the second intervention is chosen based on the measured energy expenditure and appropriate for the subject to increase energy expenditure, and wherein the first intervention is different from the second intervention.

2. The method of claim 1, wherein the first intervention is a temporary procedure.

3. The method of claim 1, wherein the first intervention is at least one selected from the group consisting of a melanocortin-4 receptor agonist therapy, activation of brown adipose tissue and a duodenal endoluminal barrier.

4. The method of claim 1, wherein the second intervention is at least one selected from the group consisting of melanocortin-4 receptor agonist therapy, activation of brown adipose tissue, gastric bypass, biliopancreatic diversion, vertical sleeve gastrectomy, adjustable gastric banding, vertical banded gastroplasty, intragastric balloon therapy, gastric plication, Magenstrasse and Mill, small bowel transposition, biliary diversion and duodenal endoluminal barrier.

5. The method of claim 1, wherein the first intervention is continued in combination with the second intervention.

6. The method of claim 1, wherein the second intervention activates the melanocortin receptor pathway in at least one cell in region selected from the group consisting of the brain, spinal cord, sympathetic nervous system, parasympathetic nervous system, enteric nervous system, gastrointestinal tract and pancreas.

7. The method of claim 1, wherein the method comprises inducing weight loss, altered energy balance or altered metabolic function in the subject.

8. A method of activating a melanocortin-4 receptor pathway in an obese subject, the method comprising:

(a) performing a first intervention on a subject, wherein the first intervention is a non-surgical procedure; and

;

(b) performing a second intervention that is distinct from the first intervention to increase energy expenditure and activate the melanocortin receptor pathway.

9. The method of claim 8, wherein the first intervention is a temporary procedure.

10. The method of claim 8, wherein the first intervention is selected from the group consisting of a melanocortin-4 receptor agonist therapy and activation of brown adipose tissue.

11. The method of claim 8, further comprises measuring melanocortin receptor pathway activation.

12. The method of claim 11, wherein the step of measuring melanocortin receptor pathway activation comprises detecting markers of melanocortin receptor activation.

13. The method of claim 8, further comprises measuring energy expenditure.

14. The method of claim 8, wherein the second intervention is at least one selected from the group consisting of melanocortin-4 receptor agonist therapy, activation of brown adipose tissue, gastric bypass, biliopancreatic diversion, vertical sleeve gastrectomy, adjustable gastric banding, vertical banded gastroplasty, intragastric balloon therapy, gastric plication, Magenstrasse and Mill, small bowel transposition, biliary diversion and duodenal endoluminal barrier.

15. The method of claim 8, wherein the method comprises inducing weight loss in the subject.

16. The method of claim 8, wherein the second intervention activates the melanocortin receptor pathway in at least one cell in region selected from the group consisting of the brain, spinal cord, sympathetic nervous system, parasympathetic nervous system, enteric nervous system, gastrointestinal tract and a pancreas.

17. A method of activating a melanocortin-4 receptor pathway to induce weight loss in an obese subject, the method comprising:

(a) performing a first intervention on a subject to affect the MC4R pathway;

(b) performing a second intervention to increase energy expenditure and activate the MC4R pathway to induce weight loss, and wherein the first intervention is different from the second intervention.

18. A method of activating a melanocortin-4 receptor pathway to induce weight loss in an obese subject, comprising:

(a) performing a first intervention on a subject to affect the MC4R pathway;

and

(b) performing a bariatric surgery to increase energy expenditure and activate the MC4R pathway to induce weight loss, and wherein the first intervention is different from the second intervention.

19. The method of claim 18, wherein the first intervention does not involve the administration to the subject of a therapeutic agent effective to activate the MC4R pathway.

20. The method of claim 18, wherein the bariatric surgery activates brown adipose tissue.