Indole lactic acid or a mixture of indole lactic acid and indole-3-propionic acid for treatment of Huntington's disease
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9636325-B2
Publication Date
2017-05-02
Expiration Date
Abstract
Indole-3-propionic acid as a marker and for treatment for Huntington Disease.
Core Innovation
The invention relates to the use of indole-3-propionic acid and indole lactic acid as gut-microbiome-derived biomarker(s) and as therapeutic risk modulator(s) for Huntington’s disease. It addresses altered levels of indole-3-propionic acid in Huntington’s disease, including decreased indole-3-propionic acid levels in Huntington’s disease humans and Huntington’s disease mouse models.
The document reports that indole-3-propionic acid levels are decreased in Huntington’s disease in CSF/plasma and in Huntington’s disease mouse models, and that these changes correlate with disease stage and can persist in an individual over time. It also links gut production changes by reporting reduced fecal indole-3-propionic acid in Huntington’s disease mice, indicating diminished gut production and a connection to commensal gut microflora.
The invention further includes analytical and quantification approaches to identify and quantify indole-3-propionic acid and electroactive indole lactic acid metabolites in urine/blood using offline/parallel LC-EC with LC-MS/MS. Therapeutic risk modulation is described in connection with increasing available indole-3-propionic acid in the gut by administering indole lactic acid or a mixture of indole-3-propionic acid and indole lactic acid, including salt, ester, protein complex, or inorganically bound preparations.
The document also states that indole-3-propionic acid measurement can be used for monitoring therapeutic efficacy and compliance and for reducing reliance on invasive sampling, including using gut microbiome metabolomic profiling from feces. Mechanistic support is provided by in vitro oxidation generation of protein-bound oxidation/adduct products involving kynuric acid intermediates, including binding to ubiquitin and angiotensin I with a covalent binding site proposed as Tyr4.
Claims Coverage
The relevant independent claim is one: clm-00001. It provides treatment coverage for Huntington’s disease by administering specific indole compounds and bound preparations to increase available indole-3-propionic acid in the gut, with dependent claim refinements covering efficacy monitoring and formulation binding mode.
Treating Huntington’s disease by administering indole lactic acid and/or indole-3-propionic acid to increase gut indole-3-propionic acid availability
Administering to an individual suffering from Huntington's disease indole lactic acid or a mixture of indole-3-propionic acid and indole lactic acid, or a salt or ester or protein complex or inorganically bound preparation thereof, with a pharmaceutically acceptable carrier, whereby to increase available levels of indole-3-propionic acid in the gut.
Monitoring efficacy via gut microbiome metabolomic profiling from feces
Monitoring the efficacy of the administration by tracking changes in indole lactic acid or indole-3-propionic acid in the gut microbiome using a metabolomic profile of an aggregate gut microbiome composition from the individual’s feces.
Formulating indole-3-propionic acid as protein-bound or inert-material-bound preparation
Administering indole-3-propionic acid bound to a protein or bound to an inert material.
Overall, the claim coverage centers on Huntington’s disease treatment by administering indole lactic acid and/or indole-3-propionic acid, including bound preparations, to increase available indole-3-propionic acid in the gut, optionally coupled with fecal gut microbiome metabolomic profiling for efficacy monitoring and with indole-3-propionic acid provided in protein-bound or inert-material-bound form.
Stated Advantages
Increases available levels of indole-3-propionic acid in the gut of an individual suffering from Huntington's disease.
Enables monitoring the efficacy of administration using gut microbiome metabolomic profiling from feces.
Reduces reliance on invasive sampling by using indole-3-propionic acid measurement/monitoring.
Documented Applications
Treating an individual suffering from Huntington’s disease by administering indole lactic acid and/or a mixture of indole-3-propionic acid and indole lactic acid to increase gut indole-3-propionic acid availability.
Monitoring therapeutic efficacy and compliance in the context of Huntington’s disease using gut microbiome metabolomic profiling from feces.
Drug development workflows that use indole-3-propionic acid and related metabolite measurement for biomarkers of efficacy/compliance and to reduce reliance on invasive sampling.
Interested in licensing this patent?