Research helped with support from CGDRT at The Institute of Child Health has provided important proof of concept that iPSC (induced pluripotent stem cell) technology can be combined with gene therapy as a treatment for CGD.
Professor Adrian Thrasher headed the work in collaboration with Dr Juan Bueren in Madrid. The research describes the successful generation of iPSC from the mouse model of X-CGD and shows that these cells are able to form cells of the blood system including functional neutrophils, the cell type affected in CGD. Furthermore the group show that they can correct the genetic defect in the iPSCs using the new gene therapy reagent designed with funding from CGDS.
Professor Thrasher explains: ‘iPSCs are cells that start off as mature adult cells, for example skin. They are then reprogrammed or induced in the laboratory to become their primitive ancestors – pluripotent stem cells. This term simply meaning that these cells are capable of producing all the different tissue types that make up our body. iPSCs are wonderful tools to study the biology of CGD and can be used to test out new ways to repair the genetic defect. They represent a disease model in a dish’.
The results showed there was no significant differences in the way iPSC generated from healthy mice and those from X-CGD mice were able to differentiate to form neutrophils. Professor Thrasher again: ‘Importantly we were able to correct the defect in the X-CGD iPSCs using our new lentiviral vector developed with funding by CGDS. These gene corrected cells were able to produce active oxidase activity indicating that the combination of these technologies is a viable way forward to treat conditions such as CGD.’
Professor Thrasher sees using CGD iPSC cell models for screening the way gene vectors work as an important step forward. ‘We will be able to test out different vector configurations in the laboratory more easily using these cells. This will be particularly useful.’
Looking to the future direction of the work the researchers have to test if transplanting the gene corrected iPSCs back into mice produces a fully working immune system capable of fighting infections. There remain many hurdles ahead before this work can be translated into benefit for patients with CGD as the process is currently very inefficient however Professor Thrasher is optimistic about the future.
‘If gene corrected iPSCs restore a functional immune system in the mice and we are able to translate our work to using human cells then there is significant therapeutic potential to treat people with CGD’.
Published paper
Generation of Functional Neutrophils from a Mouse Model of X-Linked Chronic Granulomatous Disorder Using Induced Pluripotent Stem Cells. Mukherjee S, Santilli G, Blundell MP, Navarro S, Bueren JA, Thrasher AJ. PLoS One. 2011 Mar 3;6(3):e17565.
IMPORTANT NOTE :
The information contained on this website is intended only as a guideline, not as a substitute for medical advice. Always consult your doctor if you or your child has any CGD symptoms or concerns.
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