HO-1 and CO: Fighters vs sickle cell disease?

摘要

It has been more than 60 years since sickle cell anemia (SCA) was first characterized at the molecular level by Linus Pauling. SCA occurs when thymine is substituted for adenosine in the 6th codon of the betaglobin gene, resulting in a substitution of the hydrophilic aminoacid glutamic acid by the hydrophobic amino acid valine (Hb S). SCD includes SCA and the compound heterozygous sickle hemoglobinopathies. It is one of the most common monogenetic diseases worldwide, responsible for over 80% of the significant hemoglobinopathies in the world. Remarkable progress has been achieved in the care of individuals with SCD, including the use of hydroxycarbamide (hydroxyurea), yet the only definite therapy remains limited to stem cell transplantation, and the overall life expectancy is still quite low. Development of new therapies is therefore required.The work of Belcher et al in this issue explores the therapeutic potential of CO in 2 mouse models of SCD, first shown to reduce the degree of sickling of erythrocytes in a human subject in 1963. The investigators had previously shown that inhaled CO reduced vascular stasis in transgenic sickle mice expressing beta~8 hemoglobin.