Treatment of cns conditions

Abstract

Aspects of the present invention relate to a method of treating an epileptic encephalopathy in a mammal in need thereof, comprising administering a composition comprising an effective amount of (4-benzyl-4-hydroxypiperidin-1-yl) (2,4′-bipyridin-3-yl)methanone or a pharmaceutically acceptable salt thereof to the mammal.

1 .- 27 . (canceled) 
     
     
         28 . A method of treating a seizure in a human in need thereof comprising administering to the human an effective amount of (4-benzyl-4-hydroxypiperidine-1-yl) (2,4′-bipyridine-3-yl) methanone or a pharmaceutically acceptable salt thereof, wherein the seizure is associated with Dravet Syndrome. 
     
     
         29 . The method of  claim 28 , wherein the method inhibits cholesterol 24-hydroxylase (CH24H). 
     
     
         30 . The method of  claim 28 , wherein the method reduces plasma levels of 24S-hydroxycholesterol (24HC). 
     
     
         31 . The method of  claim 28 , wherein the human is a child, a juvenile, or adult. 
     
     
         32 . The method of  claim 28 , wherein the human is 2 years of age or older. 
     
     
         33 . The method of  claim 28 , wherein (4-benzyl-4-hydroxypiperidine-1-yl) (2,4′-bipyridine-3-yl) methanone or a pharmaceutically acceptable salt thereof is administered orally as a single unit dose once daily or twice daily. 
     
     
         34 . The method of  claim 33 , wherein the single unit dose is between about 0.8 mg/kg to about 12 mg/kg. 
     
     
         35 . The method of  claim 33 , wherein the single unit dose is about 0.8 mg/kg, about 2 mg/kg, about 3 mg/kg, about 3.33 mg/kg, about 4 mg/kg, about 5 mg/kg, about 6 mg/kg, about 10 mg/kg, and about 12 mg/kg. 
     
     
         36 . The method of  claim 33 , wherein the single unit dose is between about 100 mg to about 800 mg. 
     
     
         37 . The method of  claim 33 , wherein the single unit dose is selected from the group consisting of about 100 mg, about 150 mg, about 200 mg, about 300 mg, about 400 mg, about 600 mg and about 800 mg. 
     
     
         38 . The method of  claim 28 , further comprising administering to the human an additional anti-epileptic drug. 
     
     
         39 . The method of  claim 38 , wherein the additional anti-epileptic drug is selected from the group of acetazolamide, brivaracetam, bromide, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine acetate, ethosuximide, felbamate, fosphenytoin sodium, gabapentin, lacosamide, lamotrigine, levetiracetam, lorazepam, mephenytoin, methlyphenobarbital, methosuximide, nitrazepam, oxcarbazepine, perampanel, piracetam, phenobarbital, phenytoin, pregabalin, primidone, retigabine, rufinamide, sodium valproate, stiripentol, tiagabine, topiramate, fenfluramine, vigabatrin, and zonisamide. 
     
     
         40 . A method of treating a seizure in a human in need thereof comprising administering to the human an effective amount of (4-benzyl-4-hydroxypiperidine-1-yl) (2,4′-bipyridine-3-yl) methanone or a pharmaceutically acceptable salt thereof, wherein the seizure is associated with Lennox-Gastaut syndrome. 
     
     
         41 . The method of  claim 40 , wherein the method inhibits cholesterol 24-hydroxylase (CH24H). 
     
     
         42 . The method of  claim 40 , wherein the method reduces plasma levels of 24S-hydroxycholesterol (24HC). 
     
     
         43 . The method of  claim 40 , wherein the human is a child, a juvenile, or adult. 
     
     
         44 . The method of  claim 40 , wherein the human is 2 years of age or older. 
     
     
         45 . The method of  claim 40 , wherein (4-benzyl-4-hydroxypiperidine-1-yl) (2,4′-bipyridine-3-yl) methanone or a pharmaceutically acceptable salt thereof is administered orally as a single unit dose once daily or twice daily. 
     
     
         46 . The method of  claim 45 , wherein the single unit dose is between about 0.8 mg/kg to about 12 mg/kg. 
     
     
         47 . The method of  claim 45 , wherein the single unit dose is about 0.8 mg/kg, about 2 mg/kg, about 3 mg/kg, about 3.33 mg/kg, about 4 mg/kg, about 5 mg/kg, about 6 mg/kg, about 10 mg/kg, and about 12 mg/kg. 
     
     
         48 . The method of  claim 45 , wherein the single unit dose is between about 100 mg to about 800 mg. 
     
     
         49 . The method of  claim 45 , wherein the single unit dose is selected from the group consisting of about 100 mg, about 150 mg, about 200 mg, about 300 mg, about 400 mg, about 600 mg and about 800 mg. 
     
     
         50 . The method of  claim 40 , further comprising administering to the human an additional anti-epileptic drug. 
     
     
         51 . The method of  claim 50 , wherein the additional anti-epileptic drug is selected from the group of acetazolamide, brivaracetam, bromide, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine acetate, ethosuximide, felbamate, fosphenytoin sodium, gabapentin, lacosamide, lamotrigine, levetiracetam, lorazepam, mephenytoin, methlyphenobarbital, methosuximide, nitrazepam, oxcarbazepine, perampanel, piracetam, phenobarbital, phenytoin, pregabalin, primidone, retigabine, rufinamide, sodium valproate, stiripentol, tiagabine, topiramate, fenfluramine, vigabatrin, and zonisamide.