METHODS FOR THE MODULATION OF BRAIN PROGESTAGEN SIGNALING IN THE PREVENTION AND TREATMENT OF NEUROLOGICAL DISORDERS AND NEURODEGENERATIVE DISEASES
First Claim
1. A method for treating or preventing a neurological disorder or neurodegenerative disease in a human subject in need thereof by administering to said subject a therapeutically effective amount of at least one physiologically acceptable agent, that increases blood serum and brain levels of one or more progestagen (progesterone, pregnenolone, 17α
- -hydroxypregnenolone, 17α
-hydroxyprogesterone, allopregnenolone, alloprogesterone, levonorgestrel, medroxyprogesterone, etonogestrel or other progesterone analogs).
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Abstract
The present invention relates to methods for modulating progestagen signaling for treating neurological disorders or neurodegenerative disease, or preventing or delaying its onset in individuals deemed by competent observation and testing to be susceptible thereto. Progestagens can be administered to elevate serum and brain levels of progestagens and induce neurogenesis. Progestagen therapy may prevent some of the neurodegenerative and cognitive changes associated with developmental and aging associated neurological disorders and neurodegenerative diseases. Progestagen therapy together with suppression of GnRH, kisspeptin, LH and/or FSH signaling also may be used for treating neurological disorders or neurodegenerative diseases. The invention also relates to methods for inhibiting or delaying blastulation during embryogenesis, and neurogenesis during embryogenesis, fetal, neonatal, childhood, puberty or adult life. Blocking progestagen, estrogen and/or opioid signaling with receptor antagonists will inhibit neurogenesis. The invention also relates to using progestagens in vitro to induce neurogenesis in embryonic or adult stem cells.
52 Citations
22 Claims
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1. A method for treating or preventing a neurological disorder or neurodegenerative disease in a human subject in need thereof by administering to said subject a therapeutically effective amount of at least one physiologically acceptable agent, that increases blood serum and brain levels of one or more progestagen (progesterone, pregnenolone, 17α
- -hydroxypregnenolone, 17α
-hydroxyprogesterone, allopregnenolone, alloprogesterone, levonorgestrel, medroxyprogesterone, etonogestrel or other progesterone analogs). - View Dependent Claims (2, 3, 4, 10, 11)
- -hydroxypregnenolone, 17α
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5. A method for treating or preventing a neurological disorder or neurodegenerative disease in a human subject in need thereof by promoting neurogenesis by administering to said subject a therapeutically effective amount of at least one physiologically acceptable agent that increases blood serum and brain levels of one or more progestagen (progesterone, pregnenolone, 17α
- -hydroxypregnenolone, 17α
-hydroxyprogesterone, allopregnenolone, alloprogesterone, levonorgestrel, medroxyprogesterone, etonogestrel or other progesterone analogs). - View Dependent Claims (6)
- -hydroxypregnenolone, 17α
- 7. A method for treating or preventing a neurological disorder or neurodegenerative disease in a human subject in need thereof by administering to said subject a therapeutically effective amount of at least one physiologically acceptable agent, that increases blood serum and brain levels of one or more progestagen plus decreases blood serum and brain levels of one or more of kisspeptin, GnRH, FSH and LH.
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12. A method for inhibiting blastulation during embryogenesis in a human or animal by administering to said subject an effective amount of at least one agent that blocks progesterone and/or estrogen signaling, where said agents are progesterone receptor (PR) antagonist including but not limited to RU-486;
- estrogen receptor (ER) antagonists including but limited to ICI 182,780 and/or opioid receptor (OR) antagonists including but not limited to ICI 174,864.
- View Dependent Claims (13, 14)
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15. A method for inhibiting neurogenesis during embryogenesis, fetal, neonatal, childhood, puberty or adult life in a human or animal by administering to said subject an effective amount of at least one agent that blocks PR, ER and OR signaling, where said agents are PR antagonist including but not limited to RU-486;
- ER antagonists including but limited to ICI 182,780 and/or OR antagonists including but not limited to ICI 174,864.
- View Dependent Claims (16, 17, 18)
- 19. A method for inducing neurogenesis in vitro where embryonic stem cells (ESC) are grown in media containing essential nutrients plus progestagen for sufficient time to generate neuronal cell types.
Specification