ANTICONVULSANT ACTIVITY OF STEROIDS
The present invention relates to methods of preventing, inhibiting, delaying, and/or mitigating seizures by administration of a steroid, e.g., a neurosteroid, e.g., allopregnanolone.
1 . A method of treating, reducing, and/or mitigating symptoms associated with and/or caused by traumatic brain injury, Alzheimer's disease, epilepsy, anxiety, fragile X syndrome, post-traumatic stress disorder, lysosomal storage disorders (Niemann-Pick type C disease), depression (including post-partum depression), premenstrual dysphoric disorder, alcohol craving, and smoking cessation in a subject in need thereof, comprising administration to the subject a steroid.
2 . A method of treating, reducing, and/or mitigating symptoms associated with and/or caused by epilepsy, in a subject in need thereof, comprising administration to the subject a steroid.
3 . A method of accelerating the termination or abortion of an impending seizure in a subject in need thereof, comprising administration to the subject a steroid.
4 . The method of any one of claims 1 to 3 , wherein the steroid is a neurosteroid.
5 . The method of any one of claims 1 to 4 , wherein the neurosteroid is selected from the group consisting of allopregnanolone, allotetrahydrodeoxycorticosterone, ganaxolone, alphaxolone, alphadolone, hydroxydione, minaxolone, and Althesin.
6 . The method of claim 5 , wherein the neurosteroid is allopregnanolone.
7 . The method of any one of claims 5 to 6 , wherein the steroid is formulated in a cyclodextrin.
8 . The method of any one of claims 1 to 7 , wherein the steroid is formulated in hydroxypropyl-beta-cyclodextrin, sulfobutylether-beta-cyclodextrin sodium salt, or a mixture thereof.
9 . The method of any one of claims 1 to 8 , wherein the subject is experiencing aura.
10 . The method of any one of claims 1 to 9 , wherein the subject has been warned of an impending seizure.
11 . The method of any one of claims 1 to 10 , wherein the subject is experiencing a seizure.
12 . The method of any one of claims 1 to 11 , wherein the subject has status epilepticus.
13 . The method of any one of claims 1 to 11 , wherein the subject has myoclonic epilepsy.
14 . The method of any one of claims 1 to 11 , wherein the subject suffers from seizure clusters.
15 . The method of any one of claims 1 to 14 , wherein the seizure is a tonic seizure.
16 . The method of any one of claims 1 to 14 , wherein the seizure is a clonic seizure.
17 . The method of any one of claims 1 to 16 , wherein the subject is a human.
18 . The method of any one of claims 1 to 17 , wherein the steroid is administered intramuscularly (i.m.), subcutaneously (s.c.) or intravenously (i.v.).
19 . The method of any one of claims 1 to 18 , wherein the steroid is administered at a dose in the range of about 0.25 mg/kg to about 15 mg/kg.
20 . The method of any one of claims 1 to 19 , comprising treating, reducing, and/or mitigating symptoms associated with and/or caused by epilepsy by intramuscularly (i.m.), subcutaneously (s.c.) or intravenously (i.v.) administering allopregnanolone formulated in a sulfobutylether-beta-cyclodextrin sodium salt.
21 . The method of any one of claims 1 to 20 , wherein the epilepsy is status epilepticus.
22 . A composition comprising or consisting essentially of a steroid and a cyclodextrin.
23 . The composition of claim 22 , wherein the steroid is a neurosteroid.
24 . The composition of claim 23 , wherein the neurosteroid is selected from the group consisting of allopregnanolone, allotetrahydrodeoxycorticosterone, ganaxolone, alphaxolone, alphadolone, hydroxydione, minaxolone, and Althesin.
25 . The composition of any one of claims 22 to 24 , wherein the steroid is allopregnanolone.
26 . The composition of any one of claims 22 to 25 , wherein the cyclodextrin is hydroxypropyl-beta-cyclodextrin, sulfobutylether-beta-cyclodextrin sodium salt, or a mixture thereof.
27 . The composition of any one of claims 22 to 26 , wherein the composition is formulated for intramuscular (i.m.), subcutaneous (s.c.) or intravenous (i.v.) administration.
28 . The composition of any one of claims 22 to 27 , wherein the composition comprises allopregnanolone and sulfobutylether-beta-cyclodextrin sodium salt.