Other modalities:
1. Erythropoietin:
The administration of large
dose of erythropoietin has been shown to augment HbF production. This prompted
clinical trials using recombinant human erythropoietin (rHuEPO) in thalassemia (Rund
and
Rachmilewitz, 2000). Not all patients responded to therapy but a study
concluded by Rachmilewitz et al. (1995), suggested that splenectomized patients responded
better, Butyrate and related drugs stimulate expression of the gamma-globin
genes to adequately balance the excess alpha-globin chains (Ikuta et al.,
1998).
2. Hemoglobin F Augmentation:
For
some years there has been interest in increasing γ- globin transcription
and fetal Hb (HbF) production in patients with β-hemoglobinopathies. For
patients with homozygous β- thalassemia, increased γ-globin production
and a reduction in the ratio of α-to non α-globin could reasonably be
expected to ameliorate the severity of anaemia. To this end, trials of
chemotherapeutic 5-azacytidinie (Lowrey et al., 1993) and hydroxyurea
(Fucharoen et al., 1993) have been conducted, but
myelotoxicity, fears of long term carcinogenesis, and only modest
responses to treatment have limited the clinical usefulness of these
agents, erythropoietin has also been used, but responses to this therapy
have been variable (Oliveri et al., 1992).
3. Butyrate therapy:
There
is considerable evidence that butyrate analogues induce erythroid
differentiation and stimulate HbF production in human erythroid progenitors in
vitro (Fibach et al., 1993). In humans, several fatty acids
including α aminobutyric acid, arginine butyrate, isobutyramide, sodium phenyl
butyrate and propionic acid have been shown to stimulate Hbf production,
suggesting that they may play a role in treatment of β-globin disorders (Collins
et al., 1995). L-camitine, one of the butyrate analogues, is a
water soluble molecule important in mammalian metabolism; it is essential for
the normal oxidation of fatty acids by the mitochondria. L-carnitine stabilizes
the cell membranes. Susceptibility to oxidative stress is increased in
erythrocytes in β-thalassemia major due to the free α–chains and the excess of
iron. Therefore, L-carnitine may prove to be beneficial in vivo by protecting
erythrocytes in β-thalassemic patients (Palmieri et al., 1994).
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