Methods for increasing platelet count by inhibiting biliverdin ixbeta reductase

Abstract

The present disclosure provides methods of treating a human having a disease or disorder that would benefit from increasing platelet counts. The method involves inhibiting the enzyme activity of biliverdin IXβ reductase (BLVRB) activity or inhibiting the expression of BLVRB gene.

1 .- 20 . (canceled) 
     
     
         21 . A method of treating a subject having a disease or disorder that would benefit from increasing platelet counts, the method comprising:
 administering to the subject therapeutically effective amount of an agent that inhibits biliverdin IXβ reductase (BLVRB) enzymatic activity and increases the platelet count of the subject.   
     
     
         22 . The method of  claim 21 , wherein the disease or disorder is selected from the group consisting of a decreased production of platelets, an increased breakdown of platelets, an increased use of platelets, and trapping of platelets in the spleen. 
     
     
         23 . The method of  claim 22 , wherein the decreased production of platelets is due to a condition selected from the group consisting of cancer, anemia, viral infection, chemotherapy and heavy alcohol consumption. 
     
     
         24 . The method of  claim 23 , wherein the cancer is leukemia. 
     
     
         25 . The method of  claim 22 , wherein the increased breakdown of platelets is due to a condition selected from the group consisting of pregnancy, autoimmune disease, bacterial infection and medication. 
     
     
         26 . The method of  claim 25 , wherein the autoimmune disease is selected from the group consisting of lupus and rheumatoid arthritis. 
     
     
         27 . The method of  claim 25 , wherein the medication is selected from the group consisting of heparin, quinine, sulfa-containing antibiotics and anticonvulsants. 
     
     
         28 . The method of  claim 22 , wherein the increased use of platelets is due to a thrombotic thrombocytopenic purpura condition. 
     
     
         29 . The method of  claim 22 , wherein the increased use of platelets is thrombocytopenia. 
     
     
         30 . The method of  claim 21 , wherein decreased production of platelets is caused by chemotherapy. 
     
     
         31 . The method of  claim 21 , wherein the agent is administered at a dose of about 100 mg/kg. 
     
     
         32 . The method of  claim 21 , wherein the agent is 4-((6-Chloro-2-methoxyacridin-9-yl)amino)-2-((4-methylpiperazin-1-yl)methyl)phenol. 
     
     
         33 . The method of  claim 21 , wherein the BLVRB enzymatic activity is inhibited by at least about 30% to about 100%. 
     
     
         34 . The method of  claim 21 , wherein the subject is a human. 
     
     
         35 . The method of  claim 21 , wherein the subject is an animal.