Compounds for treatment of hemolysis-and inflammasome-associated diseases
Disclosed herein are methods of treating a complication of a hemolysis and/or an inflammasome activation-associated disease comprising administering to a patient in need thereof quinine, or a derivative or salt thereof, or the combination of quinine and hemin. Also disclosed is a method of reducing alloimmunization in chronically transfused subjects, comprising administering to a patient in need thereof a therapeutically effective dose of quinine.
1 . A method of treating a vaso-occlusive crisis in a patient having sickle cell disease, comprising administering to a patient in need thereof a therapeutically effective dose of quinine base or quinine salt or a combination of quinine base or quinine salt and hemin.
2 . The method of claim 1 , wherein the patient exhibits hemolysis.
3 . The method of claim 1 , wherein the method comprises administration of a therapeutically effective dose of quinine base or quinine salt alone.
4 . The method of claim 1 , wherein the method comprises administration of a therapeutically effective dose of a combination of quinine base or quinine salt and hemin.
5 . The method of claim 1 , wherein the combination of quinine base or quinine salt and hemin inhibits inflammasome activation in innate immune cells leading to decreased inflammatory cytokine production.
6 . The method of claim 1 , wherein the inhibition by quinine base or quinine salt alone occurs in the presence of hemolysis or free heme in the blood.
7 . The method of claim 1 , wherein the inhibition by quinine base or quinine salt alone does not occur in the absence of hemolysis or free heme in the blood.
8 . The method of claim 1 , wherein the inhibition by the combination of quinine base or quinine salt and hemin does not depend on the presence of endogenous free heme in the blood.
9 . The method of claim 4 , wherein the patient exhibits low or no in vivo hemolysis.
10 . The method of claim 1 , wherein exogenous hemin is not administered.
11 . The method of claim 1 , wherein the method comprises inhibiting inflammatory cytokines production in the patient.
12 . The method of claim 1 , wherein the method comprises reducing anemia in the patient.
13 . The method of claim 1 , wherein the method comprises reducing vascular occlusion in the patient.
14 . The method of claim 1 , wherein the method comprises reducing tissue damage in injury.
15 . A method of treating a vaso-occlusive crisis in a patient having sickle cell disease, comprising administering to a patient in need thereof a therapeutically effective dose of a combination of quinine base or quinine salt and hemin, wherein the combination of quinine base or quinine salt and hemin is in a dose effective in inhibiting NLRP3 inflammasome pathway in a patient.