Method for selection of agents influencing intestinal motility disorders and pain
Inventors
Connolly, Eamonn • Kunze, Wolfgang • Bienenstock, John
Assignees
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Publication Number
US-10174388-B2
Publication Date
2019-01-08
Expiration Date
Abstract
A method is provided for evaluating agents for the treatment of different intestinal motility disorders, using distinct methodological parts related to musculature and nerves of the GI tract which communicate with the brain. In particular, the present invention provides a method for the selection of an agent effective for the treatment of an intestinal motility disorder, wherein the method comprises: a) a step of spatiotemporal (ST) mapping carried out on a gastrointestinal segment to analyze the effect of the agent on gastrointestinal motility; and b) a step of ex vivo nerve bundle recording carried out on a gastrointestinal segment to analyze the effect of the agent on mesenteric afferent nerve firing. Bacterial strains selected by the methods of the invention and the use of the bacterial strains in the treatment of intestinal motility disorders are also provided.
Core Innovation
The invention relates to a method of treating an intestinal motility disorder in a subject in need thereof by administering an amount effective to treat the intestinal motility disorder of a Lactobacillus reuteri bacterial strain that has been selected by a defined selection method. The selection method includes analysing the effect of the bacterial strain on gastrointestinal motility using a step of spatiotemporal (ST) mapping carried out on a gastrointestinal segment, and analysing the same bacterial strain for effects on mesenteric afferent nerve firing using a step of ex vivo nerve bundle recording carried out on a gastrointestinal segment.
The method links measured outcomes from gastrointestinal motility mapping and mesenteric afferent nerve firing to the selection of a specific Lactobacillus reuteri bacterial strain for treating intestinal motility disorders and associated pain. In the described selection approach, spatiotemporal (ST) mapping is used to derive migrating motor complex frequency, migrating motor complex velocity, and intraluminal peak pressure (PPr) as gastrointestinal motility parameters. Ex vivo nerve bundle recording is used to measure spontaneous firing frequency as a mesenteric afferent nerve firing readout for pain-signaling related effects.
The document also specifies newly identified and deposited Lactobacillus strains, including Lactobacillus reuteri deposited under DSMZ Accession No. DSM 17938, and connects the deposited strain designation to the treating method. The partial content describes selection outcomes that correspond to disorder-associated patterns, including bacterial strains that increase MMC velocity and/or PPr while decreasing afferent firing for constipation/colic, and bacterial strains that decrease motility parameters for IBS/diarrhea.
Claims Coverage
The independent claim is grounded in three inventive features that determine which Lactobacillus reuteri strain is administered for treatment: spatiotemporal (ST) mapping of a gastrointestinal segment to analyse effects on gastrointestinal motility, ex vivo nerve bundle recording of a gastrointestinal segment to analyse effects on mesenteric afferent nerve firing, and administration of Lactobacillus reuteri deposited under DSMZ Accession No. DSM 17938.
Spatiotemporal mapping selection for gastrointestinal motility effects
Selecting the bacterial strain using a step of spatiotemporal (ST) mapping carried out on a gastrointestinal segment to analyse the effect of the bacterial strain on gastrointestinal motility.
Ex vivo nerve bundle recording selection for mesenteric afferent nerve firing effects
Selecting the bacterial strain using a step of ex vivo nerve bundle recording carried out on a gastrointestinal segment to analyse the effect of the bacterial strain on mesenteric afferent nerve firing.
Administering a deposited Lactobacillus reuteri strain for treating intestinal motility disorders
Treating an intestinal motility disorder by administering an amount effective to treat the intestinal motility disorder of Lactobacillus reuteri, where the Lactobacillus reuteri strain has been deposited under DSMZ Accession No. DSM 17938, to a subject in need thereof.
Coverage centers on treating intestinal motility disorders using a Lactobacillus reuteri strain deposited as DSMZ Accession No. DSM 17938, selected through combined analysis of gastrointestinal motility via ST mapping and mesenteric afferent nerve firing via ex vivo nerve bundle recording.
Stated Advantages
Treats an intestinal motility disorder in a subject in need thereof.
Decreases pain signaling (as further specified in dependent claims).
Reduces transit time of material through the intestine (as further specified in dependent claims).
Documented Applications
Treating intestinal motility disorders in a subject, with effects analysed by ST mapping of gastrointestinal motility and ex vivo recording of mesenteric afferent nerve firing.
Managing disorder-associated gut/pain-related outcomes linked to migrating motor complex parameters, intraluminal peak pressure (PPr), and mesenteric afferent nerve firing, as described for constipation/colic and IBS/diarrhea patterns.
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