Lithium cholesterol compositions, including, but not limited to lithium cholesterol sulfate compositions, and methods of treatment for alzheimer's disease and neurological disorders

Abstract

In one aspect, the disclosure relates to compositions of lithium cholesterol compositions, including but not limited to lithium cholesterol sulfate compositions which are useful as therapeutic agents. The disclosure also relates to methods of making lithium cholesterol compositions and pharmaceutical compositions comprising therapeutically effective amounts of the lithium cholesterol compositions. The present disclosure also includes methods of treating one or more clinical neurological conditions with the lithium cholesterol compositions, such as Alzheimer's disease, autism spectrum disorder, bipolar disorder, or other neuropsychiatric disorders.

What is claimed: 
     
         1 . A method of treatment for a neurological disorder, the method comprising:
 administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of a pharmaceutical composition consisting essentially of a therapeutically effective amount of a lithium cholesterol, and one or more pharmaceutically acceptable carriers; wherein the lithium cholesterol has a structure having the formula:   
       
         
           
           
               
               
           
         
       
       where R is selected from —SO 3 Li, —PO 3 (Li) 2 , —(CH 2 ) n (C═O)OLi, or —(C═O)(CH 2 ) n (C═O)OLi, where n is integer selected from 1, 2, 3, 4, 5, and 6 
     
     
         2 . The method of  claim 1 , wherein the lithium cholesterol is selected from a structure having the formula: 
       
         
           
           
               
               
           
         
       
       and combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the lithium cholesterol is a structure having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method of  claim 1 , wherein the one or more solid pharmaceutically acceptable carriers is selected from the group consisting of: diluents, excipients, extenders, preservatives, antioxidants, solubilizers, emulsifiers, coloring agents, releasing agents, coating agents, sweetening agents, flavoring agents, perfuming agents, and adjuvants. 
     
     
         5 . The method of  claim 1 , wherein the pharmaceutical composition is administered orally. 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutical composition is an oral dosage formulation. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical composition is a solid, oral dosage form and the one or more pharmaceutically acceptable carriers comprise a solid pharmaceutical carrier. 
     
     
         8 . The method of  claim 1 , wherein the neurological disorder is selected from: a neurodegenerative condition, a neurodevelopment disorder, a brain injury, and other neuropsychiatric disorders. 
     
     
         9 . The method of  claim 1 , wherein the neurological disorder is selected from the group consisting of: Alzheimer's disease, autism spectrum disorder (ASD), Parkinson's disease, suicidal ideation, bipolar disorder, mood disorders, traumatic brain injury, radiation induced brain injury, amyotrophic laterals sclerosis, schizoaffective disorder, and tic disorder. 
     
     
         10 . The method of  claim 8 , wherein the neurodegenerative condition is Alzheimer's disease. 
     
     
         11 . The method of  claim 8 , wherein the neurodevelopmental disorder is Autism Spectrum disorder (ASD). 
     
     
         12 . The method of  claim 1 , wherein the neurological disorder is bipolar disorder. 
     
     
         13 . The method of  claim 1 , wherein administration of the pharmaceutical composition produces one or more of the following effects in the subject: increasing levels of inhibitory phosphorylation of GSK3β, decreasing levels of phosphorylation of tau, and decreasing levels of LPS-induced TNFα, as compared to the levels of said compounds in a subject not receiving treatment with the pharmaceutical composition. 
     
     
         14 . The method of  claim 1 , wherein administration of the pharmaceutical composition produces a greater brain to blood lithium level ratio in the subject than administration of lithium chloride. 
     
     
         15 . The method of  claim 1 , wherein administration of the pharmaceutical composition does not substantially increase lithium levels in the liver or kidney of the subject. 
     
     
         18 . The method of  claim 1 , further comprising separately administering the pharmaceutical composition with a second, separate pharmaceutical composition comprising at least one other therapeutic agent for treatment of the neurological disorder. 
     
     
         19 . The method of  claim 18 , wherein the other therapeutic agent is selected from the group consisting of: an anti-depressant, an anti-convulsant, a mood stabilizer, and a combination of two or more of the foregoing. 
     
     
         20 . The method of  claim 19 , wherein the other therapeutic agent is selected from the group consisting of: a selective serotonin reuptake inhibitor (SSRI), serotonin-noroepinephrine reuptake inhibitor (SNRI), serotonin antagonist and reuptake inhibitor (SARI), monamine oxidase inhibitor (MAOI), carboxamide, fructose derivative, triazine, a cholinesterase inhibitor, a N-methyl D-aspartate antagonist, a vitamin E, donepezil, rivastigmine, galantamine, memantine, and a combination of two or more of the foregoing.