Methods of monitoring estriol therapy

Patent metadata

Field	Value
Publication number	US-10406169-B2
Application number	US-201615563203-A
Country	US
Kind code	B2
Filing date	Mar 29, 2016
Priority date	Mar 30, 2015
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

Provided are methods for treating a neurodegenerative disease, such as multiple sclerosis, in a subject receiving a first estriol treatment regimen, comprising obtaining a measurement of the serum estriol concentration in the blood of the subject, and administering a second estriol treatment regimen to the subject if the serum estriol concentration is less than 6 ng/mL. The daily amount of estriol administered during the second estriol treatment regimen is preferably greater than the daily amount of estriol administered during the first estriol treatment regimen.

First claim

What is claimed is:

1. A method for reducing cortical gray matter atrophy in a human subject suffering from multiple sclerosis receiving a first estriol treatment regimen, comprising:
obtaining a measurement of the serum estriol concentration in the subject; and
administering a second estriol treatment regimen to the subject if the serum estriol concentration is less than 6 ng/mL;
wherein the daily amount of estriol administered during the second estriol treatment regimen is greater than the daily amount of estriol administered during the first estriol treatment regimen.

2. The method of claim 1 , wherein the first treatment regimen comprises administering to the subject, on a continuous basis throughout one or more consecutive treatment periods, about 200 μg to about 20 mg of estriol daily.

3. The method of claim 2 , wherein the first treatment regimen comprises administering to the subject, on a continuous basis throughout one or more consecutive treatment periods, about 1 mg to about 10 mg of estriol daily.

4. The method of claim 3 , wherein first treatment regimen comprises administering to the subject, on a continuous basis throughout one or more consecutive treatment periods, about 8 mg of estriol daily.

5. The method of claim 1 , wherein the second treatment regimen comprises administering to the subject, on a continuous basis throughout one or more consecutive treatment periods, about 1 mg to about 40 mg of estriol daily.

6. The method of claim 5 , wherein the second treatment regimen comprises administering to the subject, on a continuous basis throughout one or more consecutive treatment periods, about 2 mg to about 20 mg of estriol daily.

7. The method of claim 6 , wherein second treatment regimen comprises administering to the subject, on a continuous basis throughout one or more consecutive treatment periods, about 12 mg of estriol daily.

8. The method of claim 2 , wherein each treatment period of the first treatment regimen and/or second treatment regimen is at least 28 consecutive days, at least 56 consecutive days, least 84 consecutive days, at least 112 consecutive days, at least 4 consecutive weeks, at least 8 consecutive weeks, at least 12 consecutive weeks, at least 16 consecutive weeks, at least one month, at least two consecutive months, at least three consecutive months, or at least four consecutive months.

9. The method of claim 2 , wherein the continuous basis is once per day.

10. The method of claim 1 , wherein the first treatment regimen and/or second treatment regimen further comprises administering to the subject, for only a portion of each treatment period, a therapeutically effective amount of a progestogen.

11. The method of claim 10 , wherein the progestogen is selected from chlormadinone acetate, cyproterone acetate, desogestrel, dienogest, 5α-dihydroprogesterone, drospirenone, ethinodiol acetate, ethynodiol diacetate, etonogestrel, gestodene, 17-hydroxyprogesterone, levonorgestrel, medroxyprogesterone acetate (17α-hydroxy-6α-methylprogesterone acetate), megestrol, megestrol acetate (17α-acetoxy-6-dehydro-6-methylprogesterone), nestorone, nomegestrol acetate, norethindrone, norethindrone acetate, norethynodrel, norgestimate, norgestrel, progesterone, tanaproget, trimegestone, pharmaceutically acceptable salts of any of the foregoing, and any combination thereof.

12. The method of claim 11 , wherein the progestogen is norethindrone.

13. The method of claim 12 , wherein the progestogen is administered orally in a dose equal or equivalent to about 70 μg to about 7 mg of norethindrone daily.

14. The method of claim 13 , wherein the progestogen is administered orally in a dose equal or equivalent to about 700 μg of norethindrone daily.

15. A method for reducing cortical gray matter atrophy in a human subject suffering from multiple sclerosis receiving a first estriol treatment regimen, comprising:
obtaining a measurement of the serum estriol concentration in the subject; and administering a second estriol treatment regimen to the subject if the serum estriol concentration is less than 6 ng/mL;
wherein the first treatment regimen comprises:
administering orally to the subject, on a continuous basis for 84 consecutive days, 8 mg of estriol daily; and
administering orally to the subject, for 14 consecutive days of the 84 consecutive days, 0.7 mg of norethindrone daily; and
wherein the daily amount of estriol administered during the second estriol treatment regimen is greater than the daily amount of estriol administered during the first estriol treatment regimen.

16. The method of claim 15 , wherein the second treatment regimen comprises:
administering orally to the subject, on a continuous basis for 84 consecutive days, 12 mg of estriol daily; and
administering orally to the subject, for 14 consecutive days of the 84 consecutive days, 0.7 mg of norethindrone daily.

17. A method for reducing cortical gray matter atrophy in a subject suffering from multiple sclerosis and receiving a first estriol treatment regimen, comprising:
obtaining a measurement of the serum estriol concentration in the subject; and administering a second estriol treatment regimen to the subject if the serum estriol concentration is less than 6 ng/mL;
wherein the second treatment regimen comprises:
administering orally to the subject, on a continuous basis for 84 consecutive days, 12 mg of estriol daily; and
wherein administering orally to the subject, for 14 consecutive days of the 84 consecutive days, 0.7 mg of norethindrone daily; and
the daily amount of estriol administered during the second estriol treatment regimen is greater than the daily amount of estriol administered during the first estriol treatment regimen.

Assignees

• Univ California

Inventors

• Voskuhl Rhonda R

Classifications

• A61K31/565

  not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol · 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

• A61K31/567 Primary

  substituted in position 17 alpha, e.g. mestranol, norethandrolone · CPC title

• A61K31/57

  substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone · CPC title

• A61K38/13

  Cyclosporins · CPC title