Methods for Treating Autism Spectrum Disorder and Associated Symptoms

Abstract

The present disclosure relates to compositions and methods for treating autism spectrum disorder (ASD) by restoring an ASD patient's gut microbiota. These methods can be used with ASD patient with or without ongoing gastrointestinal symptoms. Provided here is a method for ASD treatment in a subject in need thereof comprising or consisting essentially of administering a therapeutic composition comprising a fecal microbe or a fecal microbiota preparation to the subject. Also provided here is a method comprises administering an antibiotic to a human subject; subjecting the human subject to a bowel cleanse; and administering purified fecal microbiota to the human subject. Further provided are evaluation and quantitative characterization of patient symptom improvements upon treatment described here.

1 . A method for treating an autism spectrum disorder (ASD) in a subject in need thereof, said method comprising administering to said subject an amount of a pharmaceutical composition effective for treating said ASD, wherein said pharmaceutical composition comprises a fecal microbe preparation, wherein said subject exhibits at least a 10% reduction in ASD symptom severity after said treatment as compared to before initiating said treatment, and based on an assessment system selected from the group consisting of Childhood Autism Rating Scale (CARS), Childhood Autism Rating Scale 2—Standard Form (CARS2-ST), and Childhood Autism Rating Scale 2—High Functioning (CARS2-HF). 
     
     
         2 . The method of  claim 1 , where said at least 10% reduction in ASD symptom severity is achieved after 2 or more weeks of initiating said treatment. 
     
     
         3 . The method of  claim 1 , where said at least 10% reduction in ASD symptom severity is maintained for at least 8 weeks after discontinuing said treatment. 
     
     
         4 . The method of  claim 1 , where said subject exhibits no gastrointestinal (GI) symptom prior to initiating said treatment. 
     
     
         5 . The method of  claim 1 , where said subject further exhibits one or more GI symptoms prior to initiating said treatment. 
     
     
         6 . The method of  claim 5 , where said subject exhibits at least a 50% reduction in GI symptom severity based on the Gastrointestinal Symptom Rating Scale (GSRS) after said treatment as compared to before initiating said treatment. 
     
     
         7 . The method of  claim 1 , where said method further comprises administering an antibiotic to said subject prior to administering said pharmaceutical composition. 
     
     
         8 . The method of  claim 1 , where said method further comprises subjecting said subject to a bowel cleanse. 
     
     
         9 . The method of  claim 1 , wherein said pharmaceutical composition is administered orally. 
     
     
         10 . The method of  claim 1 , wherein said fecal microbe preparation is lyophilized. 
     
     
         11 . The method of  claim 1 , wherein said fecal microbe preparation comprises a non-selective and substantially complete fecal microbiota from a single donor. 
     
     
         12 . The method of  claim 11 , wherein said non-selective and substantially complete fecal microbiota is supplemented with one or more viable, non-pathogenic microorganisms selected from the group consisting of  Prevotella, Desulfovibrio , Copprococcus, and  Clostridium, Bacteroides.    
     
     
         13 . The method of  claim 1 , wherein said fecal microbe preparation comprises a synthetic fecal composition of predetermined flora. 
     
     
         14 . The method of  claim 13 , wherein said predetermined flora comprises a preparation of viable flora in proportional content that resembles a normal healthy human fecal flora and comprises no antibiotic resistant populations. 
     
     
         15 . The method of  claim 1 , wherein said pharmaceutical composition is administered as a solid dosage form selected from the group consisting of capsule, tablet, powder, and granule. 
     
     
         16 . The method of  claim 1 , wherein said pharmaceutical composition is formulated as an acid resistant capsule. 
     
     
         17 . The method of  claim 1 , wherein said ASD is selected from the group consisting of autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome. 
     
     
         18 . A method for treating an autism spectrum disorder (ASD) in a subject in need thereof, said method comprising administering to said subject an amount of a pharmaceutical composition effective for treating said ASD, wherein said pharmaceutical composition comprises a fecal microbe preparation, wherein said subject exhibits at least a 10% reduction in ASD symptom severity after said treatment as compared to before initiating said treatment, and based on an assessment system selected from the group consisting of Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Vineland Adaptive Behavior Scale II (VABS-II). 
     
     
         19 . A method of reducing severity of an autism spectrum disorder in a human subject, comprising:
 (a) administering a non-absorbable antibiotic to an autistic human subject;   (b) subjecting the autistic human subject to a bowel cleanse; and   (c) administering purified fecal microbiota from a neurotypical human donor to the human subject; wherein the human subject exhibits a significant reduction in symptom severity based on an assessment system selected from the group consisting of CARS, CARS2-ST, CARS2-HF, ABC, SRS, and VABS-II, after said method as compared to before initiating the method.   
     
     
         20 . The method of  claim 19 , wherein said human subject exhibits at least a 10% reduction in ASD symptom severity after said treatment as compared to before initiating said treatment.