Melatonin in autoimmune disease
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.
1. A method of reducing seasonal worsening of MS in a subject who has MS, the method comprising:
identifying a subject who has a history of seasonal worsening of 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;
identifying the subject as having a level of melatonin below the reference level; and
administering a therapeutically effective amount of a melatonin agonist to the subject who has a level of melatonin below the reference level.
2. The method of claim 1 , 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.
3. 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).
4. The method of claim 1 , wherein the subject 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.
5. The method of claim 1 , further comprising administering a REV-ERB agonist or a ROR agonist.
6. The method of claim 1 , wherein the melatonin agonist is administered orally, nasally, intravenously, or intrathecally.
7. The method of claim 1 , comprising detecting a level of 6-sulfatoxymelatonin (6-SM).
8. A method of decreasing levels of Th17 cells or increasing levels of Tr1 cells in a subject, the method comprising:
identify a subject who has a history of seasonal worsening of 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;
identifying the subject as having a level of melatonin below the reference level; and
administering a therapeutically effective amount of a melatonin agonist to the subject who has a level of melatonin below the reference level.
9. The method of claim 8 , 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).
10. The method of claim 8 , further comprising administering a REV-ERB agonist or a ROR agonist.
11. The method of claim 8 , wherein the melatonin agonist is administered orally, nasally, intravenously, or intrathecally.
12. The method of claim 8 , comprising detecting a level of 6-sulfatoxymelatonin (6-SM).