|
Translational activities
M. Zheng, S. Cunningham, S. Ginn, M. Latham, L. Hobson, G. Logan, C. Smyth, J. Curtin and I. Alexander in collaboration with M. Wong, B. Kramer, G. McCowage, A. Kakakios and B. Bennetts
The clinical implementation of promising gene therapy strategies requires a broad skill base and appropriate organisational infrastructure, most notably facilities in which clinical grade gene delivery formulations can be produced and used in the context of clinical trials. After much hard work, and with financial support from private donors and the NSW Department of Health, we are now uniquely placed in Australia to lead the development and implementation of gene therapy approaches to the treatment of childhood disease.
We have established a collaboration with Professor Alain Fischer and his group in Paris to treat infants with a rare immune deficiency disorder known as SCID-X1. This condition and a closely related disorder, Adenosine deaminase (ADA) deficiency are the first genetic conditions for which gene therapy has demonstrated clear clinical benefit.
The promising results achieved by the French have highlighted a critical prerequisite for clinical success despite the relative inefficiency of currently available gene delivery technologies. Specifically, a selective growth advantage for genetically repaired cells within the bone marrow from which cells of the immune system arise. In SCID-X1 and ADA deficiency, this growth advantage is conferred by the nature of the disease. Unfortunately, this is not true for the majority of diseases for which gene therapy is envisaged. Accordingly, in collaboration with the CHW Oncology Research Unit we are exploring a strategy for conferring a selective growth advantage on gene-modified bone marrow cells using a gene that encodes a DNA repair enzyme called methylguanine methyltranferase (MGMT). Expression of this enzyme in bone marrow cells has the capacity to render them resistant to certain chemotherapeutic agents used in cancer treatment. Our current thinking is that this approach might first be employed to reduce the bone marrow toxicity and the associated side effects seen in children receiving chemotherapy for brain tumours. If successful in this context, then this strategy might be adapted for selective expansion of gene-repaired bone marrow cells in a number of other diseases.
|
|
