Methods and compositions for detecting and diagnosing diseases and conditions

• US 10,047,395 B2
• Filed: 06/23/2014
• Issued: 08/14/2018
• Est. Priority Date: 06/26/2013
• Status: Active Grant

• Current Assignee: Stealth BioTherapeutics, Inc. (Morningside Group Ltd.)
• Original Assignee: Stealth BioTherapeutics Corp. (Morningside Group Ltd.)
• Inventors: Wilson, D. Travis
• Primary Examiner(s): STANFIELD, CHERIE MICHELLE
• Application Number:
  US14/392,293
• Publication Number:
  US 20160194708A1
• Time in Patent Office: 1,513 Days
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2405/04 Phospholipids, i.e. phosphoglycerides
• CPC Class Codes: G01N 2560/00 Chemical aspects of mass spectrometric analysis of biological material
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

The disclosure provides methods for detecting and diagnosing diseases and conditions associated with defects in cardiolipin remodeling. In some embodiments, the present technology relates to methods for detecting the presence or amount of cardiolipin isoforms and/or the presence or amount of enzymes involved in cardiolipin remodeling.

Claims

1. A method for selecting a heart failure subject for treatment with an aromatic-cationic peptide , the method comprising:

(a) detecting levels of tafazzin (TAZ1) mRNA in a biological sample from the subject; and

(b) selecting the subject for aromatic-cationic peptide treatment where the level of TAZ1 mRNA in the biological sample from the subject is reduced about 2.5-fold compared to the normal control sample, and

(c) administering to the subject a therapeutically effective amount of the aromatic-cationic peptide, wherein the aromatic-cationic peptide is D-Arg-2′

6′

-Dmt-Lys-Phe-NH₂ or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, further comprising detecting levels of cardiolipin isoforms in a biological sample from the subject and comparing the levels of cardiolipin isoforms to those of a normal control subject, wherein the detecting levels of cardiolipin isoforms comprises chromatography, mass spectrometry, ELISA, Western blotting, immunodetection, or immunoprecipitation.

3. The method of claim 1, wherein detecting the level of TAZ1mRNA comprises RT-PCR, in situ hybridization, or Northern blotting.

4. The method of claim 1, wherein the peptide is administered daily for 6 weeks or more.

5. The method of claim 1, wherein the heart failure results from hypertension;

ischemic heart disease;

exposure to a cardiotoxic compound;

myocarditis;

thyroid disease;

viral infection;

gingivitis;

drug abuse;

alcohol abuse;

pericarditis;

atherosclerosis;

vascular disease;

hypertrophic cardiomyopathy;

acute myocardial infarction;

left ventricular systolic dysfunction;

coronary bypass surgery;

starvation;

an eating disorder;

or a genetic defect.

6. The method of claim 1, wherein the peptide is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.

7. The method of claim 1, further comprising separately, sequentially or simultaneously administering a cardiovascular agent to the subject, wherein the cardiovascular agent is selected from the group consisting of:

an anti-arrhythmia agent, a vasodilator, an anti-anginal agent, a corticosteroid, a cardioglycoside, a diuretic, a sedative, an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II antagonist, a thrombolytic agent, a calcium channel blocker, a throboxane receptor antagonist, a radical scavenger, an anti-platelet drug, a β

-adrenaline receptor blocking drug, α

-receptor blocking drug, a sympathetic nerve inhibitor, a digitalis formulation, an inotrope, and an antihyperlipidemic drug.

8. The method of claim 1, wherein the biological sample comprises tissue, a cell, or a mitochondrion from the subject.