Replacement Therapy for Natriuretic Peptide Deficiencies
AssigneePalatin Technologies, Inc.
InventorsCarl Spana, John H. Dodd, Trevor Hallam
Life of this patent
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Abstract
Use and methods of use of natriuretic peptide mimetics which bind to and activate natriuretic peptide receptor A in patients with a defect, condition, syndrome, disease or mutation resulting in a functional active ANP99-126 deficiency, for treatment or prophylaxis of cardiovascular disease, including but not limited to hypertension, acute coronary syndrome, cardiomyopathy, cardiac remodeling, left-ventricular hypertrophy, congestive heart failure, heart failure, high blood pressure and coronary artery disease, including use of mimetics with a plurality of amino acid residues and at least one amino acid surrogate of formula I: where R, R′, Q, Y, W, Z, J, x and n are as defined in the specification.
Claims22
A method of treating a patient with a functional atrial natriuretic peptide 99-126 (functional ANP) deficiency, comprising
- administering a natriuretic peptide receptor A (NPRA) agonist in an amount sufficient to achieve a concentration of NPRA agonist together with endogenous active ANP99-126, if any, of about 200 pg/mL to about 1,200 pg/mL in the serum or plasma.
A method of treating a patient with cardiovascular disease, comprising
- detecting a level of functional ANP in the patient, wherein detecting a level of functional ANP in the patient comprises detecting a level of ANP99-126 by detecting total atrial natriuretic peptide (total ANP) and pro-atrial natriuretic peptide (pro-ANP) in the patient, and subtracting the level of pro-ANP from total ANP;
- comparing the level of functional ANP in the patient to a level of functional ANP in a control;
- and
- administering an NPRA agonist to the patient if the level of functional ANP in the patient is less than the level of functional ANP in the control.
A method of treating a patient with cardiovascular disease, comprising
- detecting a level of functional ANP in the patient;
- detecting a level of pro-ANP in the patient;
- comparing the ratio of functional ANP to pro-ANP in the patient to the ratio of functional ANP to pro-ANP in a control;
- and
- administering an NPRA agonist to the patient if the ratio of functional ANP to pro-ANP in the patient compared to the ratio of functional ANP to pro-ANP in the control shows that the patient has a deficiency in functional ANP.
A method for reducing cardiac remodeling in a patient with cardiovascular disease, comprising
- detecting a level of functional ANP in the patient, wherein detecting a level of functional ANP in the patient comprises detecting a level of ANP99-126, by detecting total atrial natriuretic peptide and pro-atrial natriuretic peptide in the patient, and subtracting the level of pro-atrial natriuretic peptide from total atrial natriuretic peptide;
- comparing the level of functional ANP in the patient to a level of functional ANP in a control;
- and
- administering an NPRA agonist to the patient if the level of functional ANP in the patient is less than the level of functional ANP in the control;
- wherein the NPRA agonist is administered in an amount effective to alter the level of one or more parameters of cardiac remodeling by at least ten percent as compared to the levels of said one or more parameters prior to administering said composition, and wherein said one or more parameters are selected from the group consisting of cardiac unloading, increased glomerular filtration rate, decreased levels of aldosterone, decreased plasma renin activity, decreased levels of angiotensin II, decreased proliferation of cardiac fibroblasts, decreased left ventricular mass, decreased left ventricular hypertrophy, decreased ventricular fibrosis, increased ejection fraction, decreased left ventricular end systolic diameter, decreased pulmonary wedge capillary pressure, decreased right atrial pressure, and decreased mean arterial pressure.
Dependencies are inferred from the claim text.