Methods for treating Cushing's syndrome

Patent metadata

Field	Value
Publication number	US-11268145-B2
Application number	US-201715839666-A
Country	US
Kind code	B2
Filing date	Dec 12, 2017
Priority date	May 18, 2015
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

Methods are provided for assessing a clinical response to a glucocorticoid receptor antagonist (GRA) in a human subject and for diagnosing Cushing's syndrome.

First claim

What is claimed is:

1. A method for diagnosing and treating hypercortisolemia in a human patient suspected of suffering from hypercortisolemia, said treatment comprising administration of a glucocorticoid receptor antagonist (GRA), the method comprising:
obtaining a difference value consisting of the average of at least 20 difference results obtained from a cohort of at least 20 individuals known to have or suspected of having Cushing's syndrome, said individuals not having been administered a GRA, by measuring the differences between a first and a second amount or activity of 51 kDa FK506 binding protein (FKBPS protein) or a first and a second expression level of a gene encoding FKBPS protein measured in first and second primary cell samples, respectively, where said first samples are obtained from each of at least 20 individuals prior to, and said a second samples are obtained from each of said individuals at least 2 hours after, administration of a GRA to each of the individuals, and subtracting the second measured amount, activity, or expression from the first measured amount, activity, or expression from that individual to obtain differences from which to derive said difference value;
wherein said difference value is termed a threshold difference value if the average of the second amount, activity, or expression is at least 15% less than the average of the first amount, activity, or expression;
Selecting a human patient suspected of suffering from hypercortisolemia but whose urinary free cortisol (UFC) test results are not abnormal, said patient not having been administered a GRA;
a) measuring a first amount, or activity of 51 kDa FK506 binding protein (FKBPS protein) or a first expression level of a gene encoding FKBP5 protein in a primary cell sample from said patient, said patient not having been administered a GRA, thereby obtaining a control value from the result of said measuring; then
b) administering a GRA for treatment of hypercortisolemia to said patient; then
c) measuring a second amount or activity of FKBP5 protein or a second expression level of a gene encoding FKBP5 protein in a second primary cell sample obtained from the patient after said GRA administration, wherein said second primary cell sample is obtained at least 2 hours after said GRA administration, thereby obtaining a response value from the result of said measuring; and
d) subtracting said response value from said control value to obtain an FKBP5 difference value;
wherein an FKBP5 difference value that is equal to, or greater than the threshold difference value indicates a biochemical response to said GRA administration affecting cortisol activity in said cell samples from, and diagnoses hypercortisolemia in, the patient,
whereby hypercortisolemia is diagnosed and a clinical response to said treatment of hypercortisolemia is detected in the patient, and the method comprises continuation of said GRA administration; and
wherein, where the FKBP5 difference value is less than the threshold difference value, the method comprises administering no further medical treatment for hypercortisolemia to the patient.

2. The method of claim 1 , wherein the GRA administered to the patient is mifepristone.

Assignees

• Corcept Therapeutics Inc

Inventors

• Belanoff Joseph K
• Hunt Hazel
• Unitt John Francis
• Moraitis Andreas G

Classifications

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• G01N2333/723

  Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor · CPC title

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• G01N2333/99

  Isomerases (5.) · CPC title

• C12Y502/01008

  Peptidylprolyl isomerase (5.2.1.8), i.e. cyclophilin · CPC title