Method for diagnosing, preventing, and treating neurological diseases

Inventors

Finegold, Sydney M.

Assignees

US Department of Veterans Affairs

Publication Number

US-10130614-B2

Publication Date

2018-11-20

Expiration Date

2031-05-26

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Abstract

The invention provides for methods of treating autism associated with Desulfovibrio overgrowth in the gastrointestinal tract of a patient, said method comprising administering to the patient suffering from said autism a treatment course of aztreonam in an amount effective to treat autism in the patient, thereby treating autism.

Core Innovation

The invention provides methods for treating neurological diseases, especially autism, by targeting abnormal microorganisms in the gastrointestinal tract. The treatment involves administering antibiotics such as aztreonam, optionally with beta-lactamase inhibitors, and repopulating the gut with normal flora via probiotics or bacteriophage therapy. The invention further provides diagnostic methods based on detecting abnormal microbial populations or their toxins, as well as preventive methods including vaccination against toxin antigens.

A key focus is autism associated with Desulfovibrio overgrowth in the gastrointestinal tract. The method specifically comprises administering aztreonam in an amount effective to treat autism, optionally with beta-lactamase inhibitors and probiotics that compete with or inhibit Desulfovibrio. The invention also relates to screening for compounds that inhibit Desulfovibrio and thus inhibit autism, and methods of screening for autism by detecting Desulfovibrio presence.

The problem addressed is the disruption of normal gastrointestinal flora, often due to broad-spectrum antibiotic use, which can lead to the proliferation of pathogenic bacteria such as Desulfovibrio and Clostridium species. This microbial imbalance may produce neurotoxins or metabolic disturbances that disrupt neurological function, contributing to disorders including autism, especially regressive autism. There is a need for specific treatments that target the abnormal gut microflora, restore normal flora, and provide diagnostic and preventive measures for these neurological and gastrointestinal disorders.

Claims Coverage

The patent contains one independent claim primarily focused on a therapeutic method for autism related to Desulfovibrio overgrowth. Key inventive features involve administration of aztreonam and adjunct therapies.

Therapeutic method using aztreonam

A method of treating autism associated with Desulfovibrio overgrowth in the gastrointestinal tract by administering a treatment course of aztreonam in an amount effective to treat autism, thereby treating the condition.

Adjunctive beta-lactamase inhibitor administration

Further comprising administration of a beta-lactamase inhibitor selected from clavulanic acid, tazobactam, sulbactam, LK-157 or others, optionally administered concurrently with aztreonam to enhance efficacy.

Probiotic therapy following antimicrobial treatment

Administration of a probiotic and/or probiotic group comprising bacteria that compete with Desulfovibrio for nutrients or inhibit its growth in the intestinal tract, including a broad list of gut normal flora species in proportions resembling healthy human gut flora to repopulate and restore normal intestinal balance after antimicrobial therapy.

Definition of Desulfovibrio overgrowth

Recognition that Desulfovibrio overgrowth is an increase in the fraction of Desulfovibrio in total bacterial stool flora in autistic patients over control subjects, involving specific species such as Desulfovibrio desulfuricans, D. fairfieldensis, D. piger, D. intestinalis, and D. vulgaris, which are targeted by the treatment.

The claims focus on a method of treating autism linked to Desulfovibrio overgrowth by administering aztreonam, optionally with beta-lactamase inhibitors, combined with probiotic therapy to restore gut flora balance. The claims also detail the microbial species targeted and define the nature of the biological imbalance addressed by the treatment.

Stated Advantages

The invention enables improved neurological function in autism by inhibiting or eliminating pathogenic gastrointestinal microorganisms such as Desulfovibrio.

The antimicrobial therapy is designed to minimize systemic absorption and toxicity while maintaining efficacy in the gut.

Probiotic therapy after antibiotic treatment helps repopulate the gut with normal flora to prevent recurrence of symptoms.

Diagnostic and screening methods facilitate early and specific detection of autism-associated microbial imbalances.

Vaccination against microbial toxins provides a preventive immune response to inhibit neurological symptoms.

Documented Applications

Treatment of autism associated with Desulfovibrio overgrowth in the gastrointestinal tract of a patient using aztreonam.

Screening for compounds that inhibit Desulfovibrio to develop therapies for autism.

Screening for autism by detecting the presence of Desulfovibrio in patient samples.

Use of probiotic therapies to repopulate the gastrointestinal tract with normal flora after antimicrobial treatment.

Diagnosis of neurological or gastrointestinal disorders by detecting abnormal microbes or their toxins in gastrointestinal samples.

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