Washington University

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Boston University

Daniel S Ory

Forbes D Porter, Iii

Linda Peterson

Vanessa Xanthakis

Xuntian Jiang

Jean E Schaffer

Vasan S Ramachandran

Forbes Porter

The present disclosure provides the use of two very long chain ceramides for determining the risk of cardiovascular disease.

Ceramides for evaluating risk of cardiovascular disease

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 3&#x3b2;,5&#x3b1;,6&#x3b2;-trihydroxycholanic acid, N-(3&#x3b2;,5&#x3b1;,6&#x3b2;-trihydroxy-cholan-24-oyl)glycine, N-(3&#x3b2;,5&#x3b1;,6&#x3b2;-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.

Bile acid biomarkers for Niemann-Pick diseases, methods and uses therefor

Disclosed are methods for determining efficacy of a cyclodextrin therapy in a subject afflicted with a disorder involving oxysterol accumulation. These methods comprise: obtaining a first body fluid sample from the subject prior to cyclodextrin administration; administering cyclodextrin; obtaining at least one second body fluid sample after the cyclodextrin administration; subjecting the body fluid samples to chromatography-mass spectroscopy analysis to determine concentration of 24-hydroxycholesterol and/or cholestane-3&#x3b2;,5&#x3b1;,6&#x3b2;-triol; and determining magnitude of difference between the 24-hydroxycholesterol and/or cholestane-3&#x3b2;,5&#x3b1;,6&#x3b2;-triol concentration of the body fluid samples, whereby an increase or stabilization of 24-hydroxycholesterol concentration, or a reduction of cholestane-3&#x3b2;,5&#x3b1;,6&#x3b2;-triol concentration in the at least one second sample compared to the first sample, indicates efficacy of the cyclodextrin therapy.

Methods of determining efficacy of cyclodextrin therapy

Methods for screening or diagnosing subjects for disorders involving accumulation of one or more oxysterols such as cytotoxic oxysterol accumulation, Niemann-Pick C(NPC) disease, lysosomal storage diseases, cholesterol trafficking diseases, and neurodegenerative diseases. Also provided are methods for methods for screening or diagnosing subjects (including infants and neonatal subjects) for NPC disease, methods for monitoring the progression, remission, and clinical status of NPC disease, and methods for evaluating the efficacy of therapeutic treatment of NPC disease.

Growing community of inventors

Saint Louis, MO, United States of America

Daniel S Ory