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Fetal globin gene inducers: novel agents and new potential
Author(s) -
Perrine Susan P.,
Castaneda Serguei A.,
Chui David H.K.,
Faller Douglas V.,
Berenson Ronald J.,
Siritanaratku Noppadol,
Fucharoen Suthat
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05593.x
Subject(s) - fetal hemoglobin , globin , decitabine , inducer , fetus , thalassemia , medicine , biology , computational biology , pharmacology , gene , bioinformatics , gene expression , hemoglobin , genetics , pregnancy , dna methylation
Inducing expression of endogenous fetal globin (γ‐globin) gene expression to 60–70% of alpha globin synthesis produces β‐thalassemia trait globin synthetic ratios and can reduce anemia to a mild level. Several classes of therapeutics have induced γ‐globin expression in beta‐thalassemia patients and subsequently raised total hemoglobin levels, demonstrating proof‐of‐concept of the approach. Butyrate treatment eliminated transfusion requirements in formerly transfusion‐dependent patients with treatment for as long as seven years. However, prior generation inducers were not readily applicable for widespread use. Currently, a novel oral dual‐action therapeutic, sodium 2,2‐dimethylbutyrate, is in clinical trials, an oral decitabine formulation is under development, and agents with complementary mechanisms of action can be applied in combined regimens. Identification of three major genetic trait loci which modulate clinical severity provides avenues for developing tailored regimens. These refinements offer renewed potential to apply fetal globin induction as a treatment approach in patient‐friendly regimens that can be used worldwide.