Yannaki, E. & Stamatoyannopoulos, G. (2010). Hematopoietic stem cell mobilization strategies for gene therapy of beta thalassemia and sickle cell disease. Annals of the New York Academy of Sciences 1202: 59-63.
Though the clinical trial these two researchers are involved in does not yet have results that are ready for publication, the review of the risks they provide regarding the use of stem cell mobilization with G-CSF in patients with sickle cell is highly useful information. So, too, is the practice of pre-treating patients with hydroxyurea before administering the stem cell treatment, which the authors describe in detail and which forms the basis of the related clinical trial. Potential reduction of risks appears to be quite promising, though final results from the clinical trial and other supporting evidence will of course be required.
Ye, L., Chang, J., Lin, C., Sun, X., Yu, J. & Kan, Y. (2009). Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases. Proceedings of the National Academy of Sciences of the United States of America 106(24): 9826-30.
This research demonstrated the potential for using cells from amniotic fluid or chorionic villus sampling used in the prenatal diagnosis of a variety of genetic disorders, including sickle cell anemia, to derive induced pluripotent stem cells. These stem cells can then be used to treat any diagnosed genetic disorder, providing alternatives for parents that receive prenatal diagnoses of significant health issues. This process would also allow for treatment to begin earlier, which has benefits of increased efficacy and reduced damage as well as requiring fewer stem cells than would gene therapies used later in life.
Zou, J., Mali,...
& Cheng, L. (2011). Site-specific gene correction of a point mutation in human iPS cells derived from an adult patient with sickle cell disease. Blood 118(17): 4599-608.
These researchers used a gene-targeting plasmid with a drug-resistant gene cassette to, through several intermediaries, stimulate homologous recombination at a specific gene locus. Precise conversion rates of the targeted genes were achieved as per the researchers objectives, demonstrating the efficacy of their approach as a potential genetic therapy through selected genetic replacement. This is one of the first pieces of research to demonstrate the viability of single-nucleotide replacement as an effective and practical form of gene therapy in humans. Ongoing research to confirm and build upon these findings is called for.
Overview of Current Knowledge
From the literature review conducted above, it is clear that the knowledge surrounding gene therapies for sickle cell anemia is already quite substantial, though there are many key issues that require further investigation as these techniques progress and others emerges. Most current research focuses on stem cell therapies and methods for overcoming certain barriers to stem cell therapies or avoiding the side effects of these therapies, though other methodologies are also represented in primary research literature and in the broader reviews examined. Attitudes towards gene therapies remain highly positive, and this is clearly borne out by research that continues to provide successful results in therapies and in eliminating problems associated with these therapies. Greater practical deployment of these techniques and greater levels of coordinated research efforts will both help to continue the trend of growing knowledge and achievement in this area of study.
