Method of treating gastrointestinal diseases associated with species of genus Clostridium
Inventors
Assignees
US Department of Veterans Affairs • Government of the United States of America
Publication Number
US-9168275-B2
Publication Date
2015-10-27
Expiration Date
2021-06-05
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Abstract
The invention includes a method of treating gastrointestinal diseases associated with species of genus Clostridium such as clostridium deficit in human patients with gastrointestinal disorders having an etiological component such as a microbial agent producing a toxin where treated with an antimicrobial composition an amount effective to inhibit or eliminate the microbial agent. The antimicrobial composition in a form of probiotic mixture can be administrated alone or in combination with an antimicrobial agent, such as a bacteriophage which is specific for a bacterium producing toxin or antibiotics which are then used to eliminate or inhibit the clostridial species overgrown in a patient's gastrointestinal tract. Disorders that can be treated by the method of the invention include diarrhea or inflammatory bowel diseases such as colitis or Crohn's disease.
Core Innovation
The invention describes a method of treating gastrointestinal and neurological disorders that have an etiological component involving microbial agents, particularly species of the genus Clostridium that produce toxins. The method involves administering an antimicrobial composition in an amount effective to inhibit or eliminate the microbial agent. This antimicrobial composition may be a probiotic mixture, or administered in combination with antimicrobial agents such as bacteriophages specific for toxin-producing bacteria or antibiotics designed to eliminate or inhibit clostridial species overgrown in a patient's gastrointestinal tract.
Such gastrointestinal diseases and neurological disorders that can be treated by the invention include diarrhea, inflammatory bowel diseases such as colitis or Crohn's disease, and neurological disorders including Attention Deficit Disorder, Depression, Bipolar Disorder, Alzheimer's Disease, Parkinson's Disease, Tourette's Syndrome, Asperger's syndrome, Pervasive Development Disorder, early onset autism, Rhett's Syndrome, D-lactic acidosis, and schizophrenia. The invention also includes diagnostic methods involving detection of toxin-producing microbes or their toxins and preventative strategies including vaccination to elicit immune responses against toxin epitopes, thus preventing or limiting disease.
The invention addresses the problem that broad-spectrum antibiotic use can disrupt normal gut flora, leading to overgrowth of pathogenic, toxin-producing bacteria such as Clostridium difficile, which can cause antibiotic-associated colitis and other gastrointestinal and neurological disorders. This microbial imbalance and toxin production disrupt neurological function and contribute to disorders previously unrelated by conventional knowledge but now understood to share a common etiology involving gut microbial flora imbalance.
Claims Coverage
The patent includes two independent claims focusing on methods for treating autism associated with pathogenic bacterial colonization in the gastrointestinal tract, outlining the use of specific antimicrobial agents to alleviate autistic symptoms.
Method of treating autism with specific antimicrobials
Administering to a patient suffering from early onset autism a treatment course of an effective amount of metronidazole, bacitracin, or vancomycin to treat autism associated with colonization of pathogenic bacteria in the gastrointestinal tract and thereby alleviate autistic symptoms.
Treatment of autism following prior antimicrobial use excluding specified drugs
Administering to a patient with early onset autism, who was previously administered an antimicrobial agent different from metronidazole, bacitracin, or vancomycin, a treatment course of an effective amount of metronidazole, bacitracin, or vancomycin to alleviate autistic symptoms associated with pathogenic bacterial colonization.
The claims focus on antimicrobial treatment methods targeting autism linked to pathogenic gut bacterial colonization, particularly emphasizing the use of metronidazole, bacitracin, and vancomycin, including treatment after prior administration of other antimicrobials.
Stated Advantages
The antimicrobial composition has low systemic absorption, minimizing systemic toxicity.
It is effective in inhibiting or eliminating clostridial species responsible for toxin-mediated disorders.
Use of specific antibiotics such as ramoplanin avoids cross-resistance issues and preserves normal gut flora better than vancomycin or metronidazole.
Probiotic therapy can restore normal gut flora and limit recurrence of toxin-producing microbial overgrowth.
Vaccination to elicit gut mucosal immunity prevents neurological symptoms by neutralizing toxins locally.
The method demonstrated significant short-term improvement in autistic symptoms in children by targeting gut microbial populations.
Documented Applications
Treatment of gastrointestinal diseases such as diarrhea, antibiotic-associated diarrhea, inflammatory bowel diseases like colitis and Crohn's disease.
Treatment and prevention of neurological disorders including regressive (late onset) autism, early onset autism, Attention Deficit Disorder, Depression, Bipolar Disorder, Alzheimer's Disease, Parkinson's Disease, Tourette's Syndrome, Asperger's syndrome, Rhett's Syndrome, D-lactic acidosis, Whipple's Disease, and Schizophrenia.
Diagnostic methods detecting microbial toxins or genes related to neurotoxins in patients suspected of having neurological or gastrointestinal disorders.
Prophylactic vaccination strategies to induce gut mucosal immunity against clostridial toxins.
Use of bacteriophages specific for pathogenic bacteria to reduce toxin-producing bacterial populations.
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