Method for augmenting fetal hemoglobin

Abstract

A method is provided for inhibiting the γ to β-globin switching in subjects afflicted with β-globin disorders. The method is particularly adapted for ameliorating the clinical symptoms of sickle cell anemia by periodically introducing butyrate, .Iadd.α-amino-n-butyric acid, .Iaddend.or . .certain isomers, homologs, analogs or chemical variations thereof,.!. .Iadd.isobutyramide .Iaddend.into the bloodstream of the subject prior to natural completion of the switching process.

What is claimed is: . .1. A method for ameliorating β-globin disorders in a mammal comprising the step of introducing into the bloodstream of said mammal periodically during its gestation period and/or infancy, a compound of the formula I: ##STR3## wherein R is --CO 2  R 1 , --SO 2  R 1 , --SO 3  R 1 , or ##STR4## and R 1  is NH 2 , H, M, branched or linear alkyl 1-4 carbons or partially or perfluorinated branched or linear alkyl of 1-4 carbon atoms, and M is a cation; Z is --CH 3 , --X, or --CX 3  ; and X is H, Cl, F, Br, I or combinations thereof; Y is H, --NH 2 , --NH 3   + , --CX 3  or F; and R' is H or F; or a mixture thereof, in an amount, frequency and duration of life sufficient to inhibit or reverse fetal 
     
        γ to β-globin switching..!.. .2.  A method according to claim 1 wherein said mammal is human and said disorder is sickle cell 
     
     
        anemia..!.. ..  A method according to claim 1 wherein said mammal is human 
     
     
        and said disorder is β-thalassemia..!.4. A method . .according to claim 2 or 3 wherein said compound comprises.!. .Iadd.for ameliorating sickle cell anemia or β-thalassemia in a human comprising the step of introducing into the bloodstream of said human periodically during its gestation period and/or infancy .Iaddend.α-amino-n-butyric acid .Iadd.in an amount, frequency and duration of life sufficient to inhibit 
     
     
        or reverse fetal γ to β-globin switching.Iaddend.. 5. A method . .according to claim 2 or 3 wherein said compound comprises.!. .Iadd.for ameliorating sickle cell anemia or β-thalassemia in a human comprising the step of introducing into the bloodstream of said human periodically during its gestation period and/or infancy .Iaddend.sodium butyrate .Iadd.in an amount, frequency and duration of life sufficient to inhibit or reverse fetal γ to β-globin switching.Iaddend.. 
     
     
        . .    A method according to claim 2 or 3 wherein said compound comprises β-chloro-D-alanine..!.. .7. A method according to claim 2 or 3 wherein said compound comprises 3-chloro-proprionic acid..!.. .8. A method according to claim 2 or 3 wherein said compound comprises 5-(2-chloroethyl)tetrazole..!.. .9. A method according to claim 2 or 3 wherein said compound comprises heptafluorobutyric acid..!.. .10. A method according to claim 2 or 3 wherein said compound comprises α-aminopropanesulfonic acid..!.. .11. A method according to claim 2 or 3 wherein said compound comprises sodium propanesulfinate..!.. .12. A method according to claim 1 wherein said γ to β-globin switching is is inhibited to the extent that γ-globin synthesis in said mammal remains at 10 to 20% above normal levels after birth..!.. .13. A method according to claim 2 or 3 wherein said compound comprises 
     
     
        chloroproprionic acid..!.14. A method . .according to claim 2 or 3 wherein said compound comprises.!. .Iadd.for ameliorating sickle cell anemia or β-thalassemia in a human comprising the step of introducing into the bloodstream of said mammal periodically during its gestation period and/or infancy .Iaddend.isobutyramide .Iadd.in an amount, frequency and duration of life sufficient to inhibit or reverse fetal γ to β-globin 
     
     
        switching.Iaddend.. .Iadd.15.  The method according to any one of claims 4, 5 or 14 wherein said γ- to β-globin switching is inhibited to the extent that γ-globin synthesis in said human remains at 10 to 20% above normal levels after birth. .Iaddend.