Methods of regulating renalase (monoamine oxidase c)

Abstract

The present invention provides methods of using Monoamine Oxidase C (MAO-C), also known as renalase, as a therapeutic protein in its active and inactive forms. Administering inactive renalase protein to individuals with lower renalase levels can be used to provide them with an adequate pool of the protein that can be activated by the body as needed. Active renalase protein can be administered to individuals needing an immediate reduction of catecholamine levels. An inhibitor of renalase may be used to enhance adrenergic action.

1 . A method of preventing, treating or ameliorating a renalase-mediated condition, disorder or disease in a mammal comprising administering to said mammal a therapeutically effective amount of inactive renalase. 
     
     
         2 . The method of  claim 1 , wherein the inactive renalase is recombinantly produced. 
     
     
         3 . The method of  claim 1 , further comprising administering a cofactor for the inactive renalase. 
     
     
         4 . The method of  claim 3 , wherein the cofactor is administered either before, during or after supplying the inactive renalase. 
     
     
         5 . The method of  claim 4 , wherein the cofactor is flavin adenine dinucleotide (FAD) or its analogs. 
     
     
         6 . The method of  claim 1 , further comprising administering a catecholamine to the individual either before, during or after supplying the inactive renalase. 
     
     
         7 . The method of  claim 6 , wherein the catecholamine is one or more catecholamines selected from the group consisting of dopamine, norepinephrine, and epinephrine. 
     
     
         8 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         9 . The method of  claim 1 , wherein the inactive renalase is administered in a composition comprising a pharmaceutically-acceptable carrier, diluent or vehicle. 
     
     
         10 . The method of  claim 1 , wherein the inactive renalase is formulated for oral or injectable administration. 
     
     
         11 . The method of  claim 1 , wherein the inactive renalase is administered either before, during or after administration of active renalase. 
     
     
         12 . The method of  claim 1  or  11 , wherein the condition, disorder or disease is selected from the group consisting of a renal condition, disorder or disease; a cardiovascular condition, disorder or disease; a heart condition, disorder or disease; a central nervous system (CNS) condition, disorder or disease; pre-eclampsia; and any combination thereof. 
     
     
         13 . The method of  claim 12 , wherein the cardiovascular condition, disorder or disease is selected from the group consisting of hypertension, asymptomatic left ventricular dysfunction, chronic congestive heart failure (CHF), myocardial infarction (MI), cardiac rhythm disturbance, stroke, atherosclerosis, and any combination thereof. 
     
     
         14 . The method of  claim 13 , wherein the hypertension is selected from the group consisting of chronic hypertension, systolic hypertension, isolated systolic hypertension, diabetic hypertension, pulmonary hypertension, acute severe hypertension, and any combination thereof. 
     
     
         15 . The method of  claim 12 , wherein the renal condition, disorder or disease is selected from the group consisting of end-stage renal disease (ESRD), chronic renal failure, and any combination thereof. 
     
     
         16 . The method of  claim 12 , wherein the CNS condition, disorder or disease is selected from the group consisting of depression, anxiety, mania, schizophrenia, and any combination thereof. 
     
     
         17 . A method of supplementing an individual's endogenous renalase comprising supplying the individual with exogenous inactive renalase. 
     
     
         18 . A method of supplementing an individual's endogenous renalase comprising supplying the individual with both exogenous active and inactive renalases. 
     
     
         19 . The method of  claim 17  or  18 , further comprising administering a catecholamine to the individual. 
     
     
         20 . The method of  claim 19 , wherein the catecholamine is one or more catecholamines selected from the group consisting of dopamine, norepinephrine, and epinephrine. 
     
     
         21 . The method of  claim 19 , wherein the catecholamine is administered either before, during, or after supplying the active and inactive renalases. 
     
     
         22 . An isolated polypeptide, wherein the isolated polypeptide is inactive renalase. 
     
     
         23 . The isolated polypeptide of  claim 22  further comprising a cofactor. 
     
     
         24 . The isolated polypeptide of  claim 23  wherein the cofactor is flavin-adenosine-dinucleotide (FAD). 
     
     
         25 . A composition comprising or consisting essentially of the isolated polypeptide of  claim 22  and a pharmaceutically-acceptable carrier, diluent or vehicle. 
     
     
         26 . The composition of  claim 25 , wherein the composition is formulated for oral or injectable administration. 
     
     
         27 . The composition of  claim 25 , wherein the composition is an immediate release or a controlled release dosage form. 
     
     
         28 . The composition of  claim 25 , wherein the polypeptide is in a microcrystalline form. 
     
     
         29 . The composition of  claim 25 , wherein the polypeptide is encapsulated in nanoparticles.