# US 2017/0285015 A1 · Bile acid biomarkers for niemann-pick diseases, methods and uses therefor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2017/0285015 A1 - Document ID: US20170285015A1 - Status: Published application - Kind: A1 - Application number: 15/581,389 - Filed: 2017-04-28 - Published: 2017-10-05 - Earliest claimed: 2014-10-28 - Assignees: Washington University - Inventors: Daniel ORY; Xuntian JIANG - Web page: https://patentgrep.com/patent/US20170285015A1 ## CPC - G01N 33/5308: {for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites} - A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol - G01N 33/6848: {Methods of protein analysis involving mass spectrometry} - G01N 33/743: {Steroid hormones} - G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} - C12M 3/00: Tissue, human, animal or plant cell, or virus culture apparatus - G01N 30/7233: {interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)} - G01N 2800/04: Endocrine or metabolic disorders - G01N 2800/085: Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin - G01N 2800/28: Neurological disorders - G01N 2800/38: Pediatrics - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} ## Abstract Methods for identification and quantification of bile acids are disclosed. Bile acids in plasma, serum and/or blood such as a dried blood spot are used to identify subjects with a Niemann-Pick disease. The methods include measuring levels of a bile acid, such as 3β,5α,6β-trihydroxycholanic acid, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)glycine, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)taurine, or a combination thereof. Detection of bile acids involve mass spectroscopy and/or a combination of mass spectroscopy and liquid chromatography such as a LC-MS/MS assay. The methods can be used with sphingomyelinase assays to detect, diagnose and differentiate between Niemann-Pick A/B and Niemann-Pick C (NPC) disease. ## Claims ### Claim 1 A method of detecting a Niemann-Pick disease in a subject comprising: (a) providing a sample from a subject; (b) subjecting the sample to a liquid chromatography-mass spectroscopy analysis to determine the concentration in the sample of at least one bile acid; (c) comparing the amount of the at least one bile acid present in the sample to a reference value of the at least one bile acid obtained from a control population consisting of individuals not afflicted with a Niemann-Pick disease; and (d) diagnosing the subject as afflicted with a Niemann-Pick disease if the amount of the at least one bile acid from the subject is statistically significantly greater than that of the reference value. ### Claim 2 (depends on 1) A method in accordance with claim 1, wherein the Niemann-Pick disease is selected from the group consisting of Niemann-Pick A disease and Niemann-Pick B disease. ### Claim 3 (depends on 1) A method in accordance with claim 1, wherein the Niemann-Pick disease is Niemann-Pick C disease. ### Claim 4 (depends on 1) A method in accordance with claim 1, wherein the at least one bile acid is selected from the group consisting of 3β,5α,6β-trihydroxychoIanic acid, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)glycine, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)taurine, 5α-cholanic acid-3β,5α,6β-triol, 5α-choIanic acid-3β,5α,6β-trioI N-(carboxymethyl)-amide, and a combination thereof. ### Claim 5 (depends on 1) A method in accordance with claim 1, wherein the at least one bile acid is 5α-cholanic acid-3β,5α,6β-triol N-(carboxymethyl)-amide. ### Claim 6 (depends on 1) A method in accordance with claim 1, wherein the sample is a body fluid sample. ### Claim 7 (depends on 6) A method in accordance with claim 6, wherein the body fluid sample is selected from the group consisting of a plasma sample, a serum sample, a blood sample, a sputum sample, a urine sample, an amniotic fluid sample, cord blood, and a combination thereof. ### Claim 8 (depends on 6) A method in accordance with claim 6, further comprising adding a known amount of a bile acid internal standard to the body fluid sample. ### Claim 9 (depends on 1) A method in accordance with claim 1, wherein a Niemann-Pick disease is diagnosed if the at least one bile acid concentration is at least 2 fold greater than the reference value. ### Claim 10 (depends on 1) A method in accordance with claim 1, wherein the reference value is an average concentration of the at least one bile acid of a non-Niemann-Pick afflicted control group. ### Claim 11 A method for determining the status of a Niemann-Pick disease in a subject with a Niemann-Pick disease comprising: (a) obtaining at least one body fluid sample from the subject; (b) determining a quantification value of at least one bile acid selected from the group consisting of 3β,5α,6β-trihydroxycholanic acid, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)glycine and N-(3β,5α,6β-trihydroxy-cholan-24-oyl)taurine by subjecting the at least one body fluid sample to a liquid chromatography-mass spectroscopy analysis; and (c) determining the magnitude of the difference between the quantification value and a reference value of the at least one bile acid obtained from the subject at an earlier time, wherein if the quantification value is statistically significantly greater than or equal to the reference value, then the subject is not deemed to exhibit remission of the Niemann-Pick disease. ### Claim 12 A method of detecting a Niemann-Pick disease in a subject comprising: (a) providing a sample from a subject; (b) subjecting the sample to a mass spectroscopy analysis to determine the concentration in the sample of at least one bile acid; (c) comparing the amount of the at least one bile acid present in the sample to a reference value of the at least one bile acid obtained from a control population consisting of individuals not afflicted with a Niemann-Pick disease; and (d) diagnosing the subject as afflicted with a Niemann-Pick disease if the amount of the at least one bile acid from the subject is statistically significantly greater than that of the reference value. ### Claim 13 (depends on 12) A method in accordance with claim 12, wherein the Neimann-Pick disease is selected from the group consisting of Niemann-Pick A disease and Niemann-Pick B disease. ### Claim 14 (depends on 12) A method in accordance with claim 12, wherein the Neimann-Pick disease is Niemann-Pick C disease. ### Claim 15 (depends on 12) A method in accordance with claim 12, wherein the at least one bile acid is selected from the group consisting of 3β,5α,6β-trihydroxycholanic acid, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)glycine, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)taurine, 5α-cholanic acid-3β,5α,6β-triol, 5α-cholanic acid-3β,5α,6β-triol N-(carboxymethyl)-amide, and a combination thereof. ### Claim 16 (depends on 12) A method in accordance with claim 12, wherein the at least one bile acid is 5α-cholanic acid-3β,5α,6β-triol N-(carboxymethyl)-amide. ### Claim 17 (depends on 12) A method in accordance with claim 12, wherein the sample is a body fluid sample. ### Claim 18 (depends on 17) A method in accordance with claim 17, wherein the body fluid sample is selected from the group consisting of a plasma sample, a serum sample, a blood sample, a sputum sample, a urine sample, an amniotic fluid sample, chord blood, and a combination thereof. ### Claim 19 (depends on 17) A method in accordance with claim 17, further comprising adding a known amount of a bile acid internal standard to the body fluid sample. ### Claim 20 (depends on 17) A method in accordance with claim 17, wherein a Niemann-Pick disease is diagnosed if the at least one bile acid concentration is at least 2 fold greater than the reference value. ### Claim 21 (depends on 17) A method in accordance with claim 17, wherein the reference value is an average concentration of the at least one bile acid of a non-Niemann-Pick afflicted control group. ### Claim 22 A method for determining the status of a Niemann-Pick disease in a subject with a Niemann-Pick disease comprising: (a) obtaining at least one body fluid sample from the subject; (b) determining a quantification value of at least one bile acid selected from the group consisting of 3β,5α,6β-trihydroxycholanic acid, N-(3β,5α,6β-trihydroxy-cholan-24-oyl)glycine and N-(3β,5α,6β-trihydroxy-cholan-24-oyl)taurine by subjecting the at least one body fluid sample to a mass spectroscopy analysis; and (c) determining the magnitude of the difference between the quantification value and a reference value of the at least one bile acid obtained from the subject at an earlier time, wherein if the quantification value is statistically significantly greater than or equal to the reference value, then the subject is not deemed to exhibit remission of the Niemann-Pick disease.