Use of oxygenated cholesterol sulfates for treating neurological conditions, neurodegenerative diseases, and addiction

Abstract

Aspects of the present disclosure include methods for treating at least one of depression, neurodegenerative disease, multiple sclerosis, Parkinson's disease, spinocerebellar degeneration, Friedreich ataxia, ataxia-telangiectasia, progressive supranuclear palsy, Huntington's disease, striatonigral degeneration, olivopontocerebellar atrophy, Shy-Drager syndrome, schizophrenia, schizoaffective disorder, manic-depression (bipolar) disorder, disturbed or abnormal circadian entrainment, childhood Alice in Wonderland syndrome, childhood acute cerebellar ataxia, and Alzheimer's disease. In some instances, methods include treating an addiction to a drug, such as alcohol addiction, cocaine addiction or amphetamine addiction. In practicing the subject methods, an effective amount of at least one compound selected from 25-hydroxycholesterol-3-sulfate (25HC3S), 25-hydroxycholesterol-disulfate (25HCDS), 27-hydroxycholesterol-3-sulfate (27HC3S), 27-hydroxycholesterol-disulfate (27HCDS), 24-hydroxycholesterol-3-sulfate (24HC3S), 24-hydroxycholesterol-disulfate (24HCDS), and 24,25-epoxycholesterol-3-sulfate, or salt thereof is administered to the subject.

1 . A method of treating at least one of depression, neurodegenerative disease, multiple sclerosis, Parkinson's disease, spinocerebellar degeneration, Friedreich ataxia, ataxia-telangiectasia, progressive supranuclear palsy, Huntington's disease, striatonigral degeneration, olivopontocerebellar atrophy, Shy-Drager syndrome, schizophrenia, schizoaffective disorder, manic-depression (bipolar) disorder, disturbed or abnormal circadian entrainment, childhood Alice in Wonderland syndrome, childhood acute cerebellar ataxia, and Alzheimer's disease, in a subject in need thereof, comprising:
 administering to the subject an effective amount of at least one compound selected from 25-hydroxycholesterol-3-sulfate (25HC3S), 25-hydroxycholesterol-disulfate (25HCDS), 27-hydroxycholesterol-3-sulfate (27HC3S), 27-hydroxycholesterol-disulfate (27HCDS), 24-hydroxycholesterol-3-sulfate (24HC3S), 24-hydroxycholesterol-disulfate (24HCDS), and 24,25-expoxycholesterol-3-sulfate, or salt thereof.   
     
     
         2 . A method of treating an addiction in a subject in need thereof, the method comprising administering to the subject at least one compound selected from 25-hydroxycholesterol-3-sulfate (25HC3S), 25-hydroxycholesterol-disulfate (25HCDS), 27-hydroxycholesterol-3-sulfate (27HC3S), 27-hydroxycholesterol-disulfate (27HCDS), 24-hydroxycholesterol-3-sulfate (24HC3S), 24-hydroxycholesterol-disulfate (24HCDS), and 24,25-epoxycholesterol-3-sulfate, or salt thereof in an amount effective to reduce the addiction. 
     
     
         3 . The method of  claim 2 , wherein the addiction is at least one of drug addiction and behavioral addiction. 
     
     
         4 . The method of  claim 2  or  3 , wherein the addiction comprises drug addiction or wherein the addiction comprises addiction to a drug comprising at least one of alcohol, opioid, cocaine, and amphetamine. 
     
     
         5 . The method of  claim 4 , wherein administering the at least one compound is effective to reduce one or more of: a physiological dependence on the drug by the subject; a psychological dependence on the drug by the subject; and cravings for the drug by the subject. 
     
     
         6 . The method of any one of  claims 1  to  5 , wherein the method comprises administering to the subject an effective amount of 25-hydroxycholesterol-3-sulfate (25HC3S) or salt thereof. 
     
     
         7 . The method of any one of  claims 1  to  6 , wherein the at least one compound is administered in an amount selected from the group consisting of:
 (a) an amount ranging from 0.001 mg/kg/day to 100 mg/kg/day; 
 (b) an amount ranging from 0.1 mg/kg to 100 mg/kg, based on body mass of the subject; and 
 (c) an amount ranging from 1 mg/kg to 10 mg/kg, based on body mass of the subject. 
 
     
     
         8 . The method of any one of  claims 1  to  7 , wherein the administering is performed from once to 3 times per day. 
     
     
         9 . The method of any one of  claims 1  to  8 , wherein the administering comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection, and intramuscular injection. 
     
     
         10 . The method of any one of  claims 1  to  9 , wherein the administering comprises administering a pharmaceutical composition comprising the at least one compound and a physiologically acceptable excipient, diluent, or carrier. 
     
     
         11 . The method of  claim 10 , wherein the pharmaceutical composition is formulated in unit dosage form. 
     
     
         12 . The method of  claim 10  or  11 , wherein the pharmaceutical composition is in solid form. 
     
     
         13 . The method of any one of  claims 10  to  12 , wherein the pharmaceutical composition: (a) is in the form of a powder, a tablet, a capsule, or a lozenge; and/or (b) comprises the at least one compound in freeze-dried form together with a bulking agent. 
     
     
         14 . The method of  claim 10  or  11 , wherein the pharmaceutical composition comprises a carrier that is a liquid. 
     
     
         15 . The method of  claim 14 , wherein the at least one compound is solubilized in the liquid or dispersed in the liquid. 
     
     
         16 . The method of  claim 14  or  15 , wherein: (a) the liquid is aqueous; or (b) the liquid is sterile water for injections or phosphate-buffered saline. 
     
     
         17 . The method of any one of  claims 10  and  14  to  16 , wherein the pharmaceutical composition is in a sealed vial, ampoule, syringe, or bag.