Sickle cell anaemia - decitabine
Sickle cell anaemia is a disorder of the red blood cells in which the haemoglobin is abnormal and sticks together, forming rods. This leaves the red blood cells rigid and sickle shaped, which means they cannot squeeze through small blood vessels as easily as normal, flexible red blood cells.
Sickle cell anaemia is a disorder of the red blood cells in which the haemoglobin is abnormal and sticks together, forming rods. This leaves the red blood cells rigid and sickle shaped, which means they cannot squeeze through small blood vessels as easily as normal, flexible red blood cells.
This can result in these blood vessels becoming blocked, which can lead to severe pain and organ damage.
Decitabine is a drug that was originally developed to treat myelodysplastic syndrome by Pharmachemie. It was acquired by SuperGen in 1999, which is investigating its use in treating sickle cell anaemia, as well as in various malignancies. Its mechanism of action is believed to involve DNA hypomethylation to silence the gamma globin gene.
Eight adult patients were given doses of 0.15 to 0.30mg/kg of decitabine five days a week for two weeks.1 It was well tolerated, and levels of fetal haemoglobin (the form that depolymerises sickle haemoglobin) were significantly higher, including in those who did not respond to standard therapy with hydroxyurea. A further study over 36 weeks in seven patients was carried out, and all the patients had a significant improvement in fetal haemoglobin levels.2
In a third trial, eight patients were given 0.2mg/kg decitabine subcutaneously one to three times a week in two six-week cycles.3 Again, fetal haemoglobin levels rose significantly, and it was shown that the mechanism of action was not cytotoxic. This indicates that chronic dosing and sustained increases in fetal haemoglobin levels may well be possible, and trials continue.