System and Method for Diagnosis and Treatment

Abstract

This invention relates to a low cost rapid response diagnostic system to determine cortisol levels in patients selected as potential candidates for GCR (glucocorticoid receptor) antagonist therapy utilizing a GCR antagonist, such as ORG 34517. The rapid, sensitive, and inexpensive test can be used to determine patients who have non-normal cortisol production or disordered circadian rhythms as a method for selecting subjects for GCR antagonist therapy for whom it is likely to have beneficial and/or therapeutic effects, and can also be used to monitor changes in cortisol levels in response to treatment.

What is claimed is: 
     
         1 . A method for treating Cushing's syndrome in a patient characterized by hypercortisolism, comprising:
 selecting a patient in need of treatment for Cushing's syndrome characterized by hypercortisolism;   administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising:   at least one glucocorticoid receptor (GCR) antagonist selected from the group consisting of ORG 34517, 11-(substituted phenyl)-estra-4, 9-diene derivatives, and 11-(substituted phenyl)-estra-4, 9-diene derivatives of formula 1   
       
         
           
           
               
               
           
         
       
       wherein A is a residue of a 5- or 6-membered ring containing 2 heteroatoms which are not connected to each other and independently selected from O and S, the ring being optionally substituted with one or more halogen atoms, or A is a residue of a 5- or 6-membered ring wherein no double C—C bonds are present, containing 1 heteroatom selected from O and S, which the heteroatom is connected to the phenyl group at the position indicated with an asterisk, the ring being optionally substituted with one or more halogen atoms; R 1  is H or 1-oxo(1-4C)alkyl; R2 is H, (1-8C)alkyl, halogen or CF3; Xis selected from (H 2 OH), O, and NOH; and the interrupted line represents an optional bond; and
 at least one pharmaceutically acceptable excipient, 
 
       thereby treating Cushing's syndrome characterized by hypercortisolism in the patient. 
     
     
         2 . The method of  claim 1 , wherein the GCR antagonist is ORG 34517. 
     
     
         3 . The method of  claim 1 , wherein the pharmaceutical compound is formulated or manufactured as a liquid, elixir, aerosol, spray, powder, tablet, pill, capsule, gel, geltab, nano-suspension, nanoparticle, extended release dosage form, or topical formulation. 
     
     
         4 . The method of  claim 1 , the method further comprising:
 a) obtaining a test sample from the patient, optionally at a predetermined time, using a test sample collection unit;   b) combining said test sample with a buffering system to form a mixture in a reaction unit;   c) measuring the parameter of the mixture to determine a blank measurement;   d) combining said test sample and buffer mixture with a labeled ligand which binds cortisol, wherein the labeled ligand is provided in a label unit, in the reaction unit to produce an assay solution or combining said test sample and buffer mixture and delivering it to a carrier containing a labeled ligand which binds cortisol, wherein the labeled ligand is provided in a label unit, in the reaction unit to produce an assay immobilized complex;   e) measuring a parameter of said assay solution or complex;   f) comparing the measurement of the assay solution relative to the blank measurement;   g) comparing the measured cortisol levels to a predetermined reference range cortisol levels, wherein when the level of cortisol is elevated relative to the predetermined reference range, then the patient has Cushing's syndrome which involves elevated cortisol, which is suitable for GCR antagonist therapy;   h) administering a pharmaceutical composition comprising a GCR antagonist.   
     
     
         5 . The method of  claim 4 , wherein the GCR antagonist is ORG 34517. 
     
     
         6 . The method of  claim 4 , wherein the test sample is obtained from the patient over consecutive days. 
     
     
         7 . The method of  claim 4 , wherein the method is to determine the circadian cycle of the cortisol levels in the patient, and the predetermined time is selected from the group consisting of hourly, every 4 hours, every 6 hours, every 8 hours, and every 12 hours. 
     
     
         8 . The method of  claim 4 , wherein the predetermined reference range is a medically standard reference range. 
     
     
         9 . The method of  claim 4 , wherein the predetermined reference range is the patient's previously measured level. 
     
     
         10 . The method of  claim 4 , wherein the ligand is detectably labeled with a moiety selected from the group consisting of a radioisotope, a fluorophore, a quencher of fluorescence, an enzyme, an affinity tag, and an epitope tag. 
     
     
         11 . The method of  claim 4 , wherein said measuring of said parameter of said mixture and said assay solution is performed using a method selected from spectroscopic, photochemical, radiochemical, biochemical, enzymatic, immunochemical, chemical label displacement, surface plasmon resonance, fluorescence resonance energy transfer, fluorescence quenching, lateral flow, and fluorescence polarization means.