Melatonin in autoimmune disease

Patent metadata

Field	Value
Publication number	US-2017333371-A1
Application number	US-201515525375-A
Country	US
Kind code	A1
Filing date	Nov 12, 2015
Priority date	Nov 12, 2014
Publication date	Nov 23, 2017
Grant date	—

Abstract

Methods for treating, or reducing risk of developing, seasonal worsening of multiple sclerosis (MS) in a subject who has MS, comprising administering a melatonin agonist to a subject.

First claim

1 . A method of treating, or reducing risk of developing, multiple sclerosis (MS), or seasonal worsening of MS in a subject who has MS, the method comprising administering to a subject in need thereof a therapeutically effective amount of a melatonin agonist.

2 . The method of claim 1 , further comprising detecting a level of melatonin in a sample from a subject;
comparing the level of melatonin in the sample to a reference level of melatonin that represents a level of melatonin in a control subject who has an increased risk of having or developing seasonal worsening of MS; and identifying the subject as having an increased risk of having or developing seasonal worsening of MS when the level of melatonin in the sample is below the reference level.

3 . The method of claim 2 , wherein the reference level of melatonin is or corresponds to 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, or 24 ng/mg creatinine.

4 . The method of claim 1 , wherein the melatonin agonist is ramelteon ((S)—N-[2-(1,6,7, 8-tetrahydro-2H-indeno[5,4-b] furan-8-yl)ethyl]propionamide), agomelatine (N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide), tasimelteon ((1R, 2R)—N-[2-(2,3-dihydrobenzofuran-4-yl)cyclopropylmethyl]propanamide), or TIK-301 (LY-156735) (N-[(2R)-(6-Chloro-5-methoxy-1H-indol-3-yl)propyl]acetamide).

5 . The method of claim 1 , wherein the subject has a history of seasonal worsening of MS, has one or more symptoms associated with seasonal worsening of their MS, has low melatonin levels, lives in a climate where a low-melatonin season is occurring or about to occur, or lives in a climate where melatonin levels are typically low

6 . The method of claim 1 , further comprising administering a REV-ERB agonist or a ROR agonist.

7 . The method of claim 1 , wherein the melatonin agonist is administered orally, nasally, intravenously, or intrathecally.

8 . (canceled)

9 . (canceled)

10 . (canceled)

11 . (canceled)

12 . (canceled)

13 . (canceled)

14 . (canceled)

15 . A method of identifying a subject for treatment with a melatonin agonist for reducing risk of developing, seasonal worsening of multiple sclerosis (MS), the method comprising:
selecting a subject who has MS; detecting a level of melatonin in a sample from the subject; comparing the level of melatonin in the sample to a reference level of melatonin that represents a level of melatonin in a control subject who has an increased risk of having or developing seasonal worsening of MS; identifying the subject as having an increased risk of having or developing seasonal worsening of MS when the level of melatonin in the sample is below the reference level; and optionally administering a melatonin antagonist to the subject.

16 . The method of claim 15 , wherein the reference level of melatonin is or corresponds to 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, or 24 ng/mg creatinine.

17 . The method of claim 15 , wherein the melatonin agonist is ramelteon ((S)—N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b] furan-8-yl)ethyl]propionamide), agomelatine (N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide), tasimelteon ((1R, 2R)—N-[2-(2,3-dihydrobenzofuran-4-yl)cyclopropylmethyl]propanamide), or TIK-301 (LY-156735) (N-[(2R)-(6-Chloro-5-methoxy-1H-indol-3-yl)propyl]acetamide).

18 . The method of claim 15 , wherein the subject has a history of seasonal worsening of MS, has one or more symptoms associated with seasonal worsening of their MS, has low melatonin levels, lives in a climate where a low-melatonin season is occurring or about to occur, or lives in a climate where melatonin levels are typically low

19 . The method of claim 15 , further comprising administering a REV-ERB agonist or a ROR agonist.

20 . The method of claim 15 , wherein the melatonin agonist is administered orally, nasally, intravenously, or intrathecally.

21 . A method of decreasing levels of Th17 cells or increasing levels of Tr1 cells in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a melatonin agonist.

22 . The method of claim 21 , wherein the melatonin agonist is ramelteon ((S)—N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b] furan-8-yl)ethyl]propionamide), agomelatine (N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide), tasimelteon ((1R, 2R)—N-[2-(2,3-dihydrobenzofuran-4-yl)cyclopropylmethyl]propanamide), or TIK-301 (LY-156735) (N-[(2R)-(6-Chloro-5-methoxy-1H-indol-3-yl)propyl]acetamide).

23 . The method of claim 21 , wherein the subject has an autoimmune disease.

24 . The method of claim 23 , wherein the subject has Multiple Sclerosis, Irritable Bowel Disease, Crohn's disease, spondyloarthritides, Systemic Lupus Erythematosus, Vitiligo, rheumatoid arthritis, psoriasis, Sjögren's syndrome, or diabetes.

25 . The method of claim 21 , further comprising administering a REV-ERB agonist or a ROR agonist.

26 . The method of claim 21 , wherein the melatonin agonist is administered orally, nasally, intravenously, or intrathecally.

27 . The method of claim 2 , comprising detecting a level of 6-sulfatoxymelatonin (6-SM).

Assignees

• The Brigham And Women`S Hospital Inc
• Brigham & Womens Hospital Inc

Inventors

• Farez Mauricio
• Quintana Francisco J
• Correale Jorge

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title