10 Current status of stem cell therapy and prospects for gene therapy for the disorders of globin synthesis

Sickle cell anaemia and β-thalassaemia are today curable through the use of stem cell transplantation. Nevertheless, the disadvantages inherent in stem cell transplantation underscore the need for better therapies. A recent finding of potentially major importance is that complete eradication of host haematopoiesis is not an absolute requirement for achieving therapeutic effects in thalassaemia and sickle cell anaemia. Future stem cell transplantation protocols will use less toxic conditioning regimens in an effort to achieve a state of stable mixed chimerism between donor and host haematopoietic elements. An improved understanding of globin gene regulation and stem cell biology will allow for the first gene therapy trials for sickle cell anaemia and β-thalassaemia in the relatively near future. Initial gene therapy protocols will emphasize safety, are likely to target progenitor cells, and will involve repeated cycles of mobilization, transduction and reinfusion, with little or no conditioning. These first generation gene therapy trials are unlikely to confer major therapeutic benefits, but will provide the foundation upon which subsequent, more effective protocols will be based.