A long-sought goal in genetics has been to develop therapies that can use correctly functioning genes to replace genes with defects. If we had the technology to predictably modify our genomes, we would have the ability to cure many diseases instead of having to place people on medications for their entire lives.
For a long time, gene therapy has remained an elusive dream. But, in the past few years the dream has come closer to reality, especially in the case of ten children, who live because of researchers who kept that dream in sight (1).
Figure 1. Random children
The genetically modified children that I’m writing about, suffer from a disease called Adenosine Deaminase (ADA) deficiency. Adenosine deaminase normally acts in a biochemical pathway that breaks down nucleotides. Defects in this gene can lead to the build up of toxic compounds that kill T cells, an important component of the immune system. Without T cells, children with ADA are unable to fight off disease, and consequently live very short, challenging lives.
ADA deficiency has long been a target for scientists interested in gene therapy for multiple reasons. Helping these children is an important goal of course, but this disease has also been an attractive target because children with ADA can be treated through bone marrow transplants (2). Bone marrow, with the right characteristics from a healthy donor, contains stem cells that can develop into T cells and provide an immune response. We have learned how to genetically engineer bone marrow cells. This made the idea of genetic modifications through bone marrow transplants, and using this method to treat children with ADA, an achievable goal.
Still, it has taken several years since researchers first started working on this problem to see a clear, lasting, success.
In January, researchers published the results of a long-term study (1) demonstrating that gene therapy increased the immune functioning in nine of the ten children with ADA deficiency, who were treated in the study. All ten children are alive in a median time of 4 years after treatment. Most promising, in five of the children, the normal immune functions have been restored.
- A. Aiuti, F. Cattaneo, S. Galimberti, U. Benninghoff, B. Cassani, L. Callegaro, S. Scaramuzza, G. Andolfi, M. Mirolo, I. Brigida, A. Tabucchi, F. Carlucci, M. Eibl, M. Aker, S. Slavin, H. Al-Mousa, A. Al Ghonaium, A. Ferster, A. Duppenthaler, L. Notarangelo, U. Wintergerst, R. H. Buckley, M. Bregni, S. Marktel, M. G. Valsecchi, P. Rossi, F. Ciceri, R. Miniero, C. Bordignon, M.-G. Roncarolo (2009). Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency New England Journal of Medicine, 360 (5), 447-458 DOI: 10.1056/NEJMoa0805817
- D. B. Kohn, F. Candotti (2009). Gene Therapy Fulfilling Its Promise New England Journal of Medicine, 360 (5), 518-521 DOI: 10.1056/NEJMe0809614