Use of inosine for the treatment of t-reg deficiency
Inventors
Roos, Stefan • Liu, Yuying • He, Baokun • Rhoads, Jon Marc
Assignees
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Publication Number
US-11602551-B2
Publication Date
2023-03-14
Expiration Date
Abstract
The present invention provides the use of inosine in the treatment of a disease associated with Treg deficiency or Treg dysfunction, in particular immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX). In one embodiment of the invention, the inosine can be provided in the form of a bacterial strain that is capable of stimulating the production of inosine. Methods for stimulating the production of inosine in a subject using said strains are also provided, as are methods for the selection of a bacterial strain capable of stimulating inosine production in a subject.
Core Innovation
The document describes treatment and selection concepts centered on inosine for Treg deficiency/dysfunction, including immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) and IPEX-like syndromes. It reports that inosine administration and administration of a lactic acid bacterial strain, especially Lactobacillus reuteri, to scurfy (Foxp3) mice prolongs survival, suppresses autoimmunity and inflammation, and improves intestinal histology.
The document further reports that the approach reduces T helper 1 (TH1) and T helper 2 (TH2) cytokines, including IFN-γ and IL-4, and reduces frequencies associated with TH1/TH2 responses. It also describes mechanistic and biomarker-related findings linking Lactobacillus reuteri to restoration or increase of plasma inosine, including fecal inosine changes and metabolomic profiling.
In addition, the document describes that inosine suppresses TH1/TH2 differentiation without inhibiting lymphocyte proliferation in vitro. It also outlines a bacterial-strain selection approach based on administering candidate lactic acid bacterial strains to an animal model and measuring inosine in plasma and/or gastrointestinal samples to select strains that stimulate in vivo inosine production.
Claims Coverage
The document contains one independent claim. The independent claim is supported by dependent claim refinements that specify animal model, sample type, comparative measurement, and strain-specific exclusions or processing.
In vivo selection of a lactic acid bacterial strain by measuring inosine stimulation
An in vivo method for selecting a lactic acid bacterial strain capable of stimulating inosine production by administering a bacterial strain to a suitable animal model, obtaining samples, measuring the levels of inosine in the sample, and selecting a bacterial strain which has the ability to stimulate inosine production in vivo.
Overall claim coverage focuses on an in vivo selection method in which candidate lactic acid bacterial strains are administered to an animal model, sample collection is performed, inosine levels are measured, and strains are selected based on their ability to stimulate in vivo inosine production.
Stated Advantages
Prolongs survival in scurfy (Foxp3) mice.
Suppresses autoimmunity and inflammation.
Improves intestinal histology.
Reduces TH1/TH2 cytokines including IFN-γ and IL-4 and reduces TH1/TH2-associated frequencies.
Increases or restores plasma inosine, with fecal inosine changes.
Documented Applications
Selecting a lactic acid bacterial strain capable of stimulating inosine production by administering candidate strains to an animal model and measuring inosine levels in collected samples.
Treatment using inosine administration and/or administration of a lactic acid bacterial strain, especially Lactobacillus reuteri, in scurfy (Foxp3) mice with Treg deficiency/dysfunction including IPEX/IPEX-like syndromes.
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