Compositions and methods useful in detecting and diagnosing multiple sclerosis
Inventors
Feinstein, Douglas • Boullerne, Anne
Assignees
US Department of Veterans Affairs • University of Illinois System
Publication Number
US-12077812-B2
Publication Date
2024-09-03
Expiration Date
2042-04-07
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Abstract
Disclosed herein, are methods of detecting multiple sclerosis in a subject by measuring relative abundances of multiple oral microbiota in sample. Also, disclosed herein are methods of treatment and prophylaxis of MS.
Core Innovation
The invention provides methods of diagnosing multiple sclerosis (MS) in a subject by obtaining a biological sample, specifically saliva, and detecting an increased abundance of bacteria from the genus Gemella, Staphylococcus, or Streptococcus, and a decreased abundance of bacteria from the genus Haemophilus, Campylobacter, or Prevotella_2 compared to a control subject's sample. This microbial signature in saliva serves as a diagnostic indicator of MS.
In addition to diagnosis, the invention discloses methods of treating MS by administering to the subject a disease-modifying therapy and/or a salivary microbiome altering agent that supports the growth of beneficial bacteria (Haemophilus, Campylobacter, Prevotella_2) and reduces the growth of bacteria associated with MS (Gemella, Staphylococcus, Streptococcus). Methods for measuring the probability of developing MS based on the relative abundance of these oral microbes are also described.
The technical problem being addressed is the need for better, rapid, non-invasive diagnostics to detect onset of MS, monitor disease progression and therapeutic efficacy, and provide prognostic tools. The invention offers a novel microbiological diagnostic method using easily accessible oral samples with distinct microbial patterns that correlate with MS presence and severity, aiding early diagnosis and personalized treatment.
Claims Coverage
The patent discloses one independent claim focusing on a method of diagnosing and treating multiple sclerosis using detection of specific oral bacterial genera and subsequent administration of disease-modifying therapies.
Diagnosis of MS using oral microbiome microbial abundance changes
The method involves obtaining a saliva sample from a subject and detecting an increased abundance of Gemella, Staphylococcus, and Streptococcus genera and a decreased abundance of Haemophilus, Campylobacter, and Prevotella_2 genera relative to a control subject's saliva, thereby diagnosing MS.
Treatment of MS with disease-modifying therapy following diagnosis
Following diagnosis based on microbial abundance shifts, administering a disease-modifying therapy selected from interferon beta-1a, interferon beta-1b, glatiramer acetate, ofatumumab, peginterferon beta-1a, teriflunomide, monomethyl fumarate, dimethyl fumarate, fingolimod, cladribine, siponimod, diroximel fumarate, ozanimod, alemtuzumab, mitoxantrone, ocrelizumab, or natalizumab.
Use of salivary microbiome altering agents to support beneficial bacterial growth
The method optionally includes administering a salivary microbiome altering agent that supports the growth of Haemophilus, Campylobacter, or Prevotella_2 genera in the saliva of the MS diagnosed subject.
Determination of relative bacterial abundance by nucleic acid sequencing
The relative abundance of the disclosed bacterial genera is determined using nucleic acid sequencing techniques such as 16S rRNA amplicon sequencing or quantitative PCR.
Use of various assays to detect microbial abundance changes
Detection methods for increased or decreased abundance include nucleic acid sequencing, PCR amplification, competitive or non-competitive binding assays, radioimmunoassays, immunohistochemistry, ELISA, sandwich assays, gel diffusion immunodiffusion assays, agglutination assays, dot blotting, fluorescent immunoassays like FACS, chemiluminescence immunoassays, immunoPCR, protein A/G immunoassays, and immunoelectrophoresis assays.
The claims collectively cover a diagnostic and therapeutic method for multiple sclerosis based on identification of specific oral bacterial genera abundance changes using sequencing or immunoassays, combined with administration of disease-modifying therapies and/or microbiome altering agents to treat MS.
Stated Advantages
Provides a rapid, non-invasive, and easy to use diagnostic method for early detection of MS before clinical symptoms worsen.
Enables monitoring of disease progression and therapeutic efficacy via oral microbiome analysis.
Offers a prognostic tool to estimate disease duration or severity based on microbial abundance patterns.
Facilitates personalized treatment approaches by adjusting the oral microbiome and using disease-modifying therapies.
Documented Applications
Diagnosis of multiple sclerosis and related demyelinating disorders including neuromyelitis optica, acute disseminated encephalomyelitis, clinically isolated syndrome, and radiologically isolated syndrome.
Measuring the probability of a subject developing or having MS or MS flare-ups by analyzing relative abundances of specific oral microbiota in saliva samples.
Treatment or prophylaxis of MS by administering disease-modifying therapies and/or salivary microbiome altering agents that modulate growth of specific oral bacteria.
Use of oral microbiome profiles to distinguish clinical subtypes or disease stages of MS, such as relapsing remitting versus primary progressive forms.
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