New therapies in sickle cell disease.

CONTEXT

New therapies have evolved from our improved understanding of the biology of sickle cell disease (SCD) and the availability of a useful transgenic animal model. Several therapeutic options are available that interrupt the sickling process at various key pathways. Nitric oxide (NO)is a critical factor in the pathophysiology of SCD and is a promising antisickling agent with vasodilation properties. NO regulates blood vessel tone, endothelial adhesion, and the severity of ischaemia-reperfusion injury and anaemia in SCD. Although NO is difficult to administer, its precursor, L-arginine, is an oral supplement.

STARTING POINT

J R Romero and colleagues recently demonstrated in sickle transgenic mice that oral arginine supplementation induced NO production and reduced red-cell density by inhibiting the Gardos channel, which modulates cell hydration and polymerisation of haemoglobin S (Blood 2002; 99:1103-08). Haemoglobinopathies can be cured by stem-cell transplantation. This therapy is now accepted treatment in symptomatic children. However, most patients lack a genotypically identical family donor. G La Nasa and colleagues demonstrated unrelated-donor stem-cell transplantation may give similar results to related-donor stem-cell transplantation when extended phenotypic matching is used (Blood 2002; 99: 4350-56). This pilot study offers the possibility of cure to patients without a family donor.

WHERE NEXT

Although potential opportunities to prevent morbidity in SCD through new therapies are exciting, most patients do not have access to standard multidisciplinary specialty care. Patients require both.