Methods of Treating Sickle Cell Disease and Related Disorders Using Fumaric Acid Esters

Abstract

Methods of using one or more fumaric acid esters or pharmacologically active salts, derivatives, analogues, or prodrugs thereof to increase expression of fetal hemoglobin (HbF) are disclosed. The methods typically include administering to a subject an effective amount of one or more fumaric acid esters optionally in combination or alternation with hydroxyurea to induce HbF expression in the subject in an effective amount to reduce one or more symptoms of a sickle cell disorder, a hemoglobinopathy, or a beta-thalassemia, or to compensate for a genetic mutation is the human beta-globin gene (HBB) or an expression control sequence thereof. Pharmaceutical dosage units and dosage regimes for use in the disclosed methods are also provided.

1 - 15 . (canceled) 
     
     
         16 . A method for treating a hemoglobinopathy, a sickle cell-related disorder, or a beta thalassemia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a prodrug of monomethylfumarate. 
     
     
         17 . The method of  claim 16 , which is a method for treating a hemoglobinopathy. 
     
     
         18 . The method of  claim 17 , wherein the hemoglobinopathy is a sickle cell disorder. 
     
     
         19 . The method of  claim 18 , wherein the sickle cell disorder is sickle cell anemia. 
     
     
         20 . The method of  claim 16 , which is a method for treating a beta thalassemia. 
     
     
         21 . The method of  claim 16 , which is a method for treating a sickle cell-related disorder. 
     
     
         22 . The method of  claim 21 , wherein the sickle cell-related disorder is a retinopathy. 
     
     
         23 . The method of  claim 16 , wherein the method further comprises administering hydroxyurea to the subject. 
     
     
         24 . The method of  claim 23 , wherein the subject is unresponsive to treatment with hydroxyurea alone. 
     
     
         25 . The method of  claim 24 , wherein the subject expresses lower levels of OCTN1 than patients who respond to hydroxyurea. 
     
     
         26 . The method of any one of  claims 16 - 25 , wherein the administering of the prodrug of monomethylfumarate is orally. 
     
     
         27 . The method of  claim 22 , wherein the administering of the prodrug of monomethylfumarate is locally to the eye.