Gut-selective sequestering agents for the treatment and prevention of autism and related disorders

Abstract

The present disclosure describes methods and compositions for the treatment of neurological disorders and related symptoms by the in vivo sequestration and excretion of microbial metabolites. These metabolites are related to neurological disorders such as autism and Parkinson's disease, as well as intestinal hyperpermeability (leaky gut) and gastrointestinal comorbidities associated with such disorders.

1 - 14 . (canceled) 
     
     
         15 . A method of reducing the amount of one or more intestinal metabolites in the digestive tract of a subject exhibiting a behavioral symptom of a neurological disorder, the method comprising:
 administering to the subject a sequestrant composition which binds to at least a fraction of the at least one intestinal metabolite present in the digestive tract of the subject to form a sequestrant-metabolite complex, such that the sequestrant-metabolite complex is eliminated from the digestive tract,   wherein the sequestrant composition comprises a multiplicity of biocompatible particles which are non-absorbable by the digestive tract of the subject; and   wherein reducing the amount of one or more intestinal metabolites in the digestive tract of the subject alleviates the behavioral symptom.   
     
     
         16 . The method of claim  1 , wherein the neurological disorder is associated with intestinal hyperpermeability. 
     
     
         17 . The method of claim  1 , wherein the neurological disorder is associated with intestinal dysbiosis 
     
     
         18 . The method of claim  1 , wherein the neurological disorder is autism spectrum disorder (ASD). 
     
     
         19 . The method of claim  1 , wherein the one or more intestinal metabolites comprises 4-ethylphenyl sulfate. 
     
     
         20 . The method of claim  1 , wherein the one or more intestinal metabolites comprises 3-indoxyl sulfate. 
     
     
         21 . The method of claim  1 , wherein the one or more intestinal metabolites is selected from the group consisting of 4-ethylphenol, p-cresol, p-cresyl sulfate, indole, and 3-hydroxy indole. 
     
     
         22 . The method of claim  1 , wherein the intestinal metabolite is associated with the development or presence of the behavioral symptom. 
     
     
         23 . The method of  claim 22 , wherein the behavioral symptom comprises clinical irritability. 
     
     
         24 . The method of  claim 22 , wherein the behavioral symptom comprises communicative symptoms. 
     
     
         25 . The method of  claim 22 , wherein the behavioral symptom is selected from the group consisting of repetitive behaviors, stereotyped behaviors, obsessive behaviors, and depression. 
     
     
         26 . The method of claim  1 , wherein administering the sequestrant composition comprises administering a therapeutically effective amount of the sequestrant composition. 
     
     
         27 . The method of  claim 26 , wherein the therapeutically effective amount is effective to alleviate the behavioral symptom. 
     
     
         28 . The method of  claim 26 , wherein the therapeutically effective amount is 35 mg to 35 g per day. 
     
     
         29 . The method of  claim 27 , wherein the behavioral symptom is clinical irritability. 
     
     
         30 . The method of claim  1 , wherein the behavioral symptom is clinical irritability, and the one or more intestinal metabolites comprises 4-ethylphenyl sulfate. 
     
     
         31 . The method of claim  1 , wherein the behavioral symptom is clinical irritability, and the one or more intestinal metabolites comprises 3-indoxyl sulfate. 
     
     
         32 . The method of claim  1 , wherein said administration is oral administration.