Why, after decades of clinical trials, is gene therapy still not a widely used or successful treatment? The idea of gene therapy is to treat disease by supplementing or altering genes in an individual’s cells – replacing a mutated gene with a functional one, or expressing a therapeutic protein to act as a “drug” to treat the patient’s disease.
The objective of gene therapy may sound simple enough, but it is a complex field which has encountered many unexpected problems and setbacks. The complicated nature of gene therapy can be illustrated by one particular clinical trial carried out in France in 2000. Ten children with severe combined immunodeficiency (SCID), an immune disorder which causes victims to be extremely vulnerable to infection, took part in the gene therapy trial. The children had some of their bone marrow removed and cultured with the “normal” version of the dysfunctional SCID gene. The cells were then injected back into the patients, resulting in nine out of the ten children showing significant improvements over two years. However, three of the children later developed leukaemia, a blood cancer, and one died. It was discovered that in some of the children, the “normal” SCID gene had been inserted next to a gene involved in the development and proliferation of blood cells. This led to the development of blood cancer, an unforeseen risk of the gene therapy treatment.
Gene therapy also does not hold much potential as a therapy for genetic disorders which are caused by the combined effects of a number of gene mutations. These are called multigene disorders, and include some of the most commonly occurring diseases such as diabetes and Alzheimers. The best candidates for gene therapy are disorders which are traceable to a single defective gene, but even these have their drawbacks. Cystic fibrosis is a lung condition caused by defective epithelial cells in the lungs. These epithelial cells are the main target for gene therapy, but these cells are constantly being renewed in the body so the therapy is short-lived and not a long term solution. What’s more, cells in the bile duct and pancreas also cause problems in cystic fibrosis, but these cells are unaffected by gene therapy treatments on lung epithelial cells. This means that, even with a disorder caused by one gene mutation, gene therapy cannot resolve all symptoms of a genetic disease.
Ethical issues surrounding gene therapy further contribute to its lack of success. Interfering with the genetic make-up of humans, even in the short term, is considered to be unacceptable by some. Religious organisations can consider it to be “playing God”, and may be of the opinion that gene therapy is never permissible.
Science has advanced hugely in the time since gene therapy trials began, and many new trials are currently in the pipeline. If the uncertainty of patient’s outcomes can be addressed, perhaps gene therapy can become more widely accessible to patients in the coming years.
(To find out more about the SCID gene therapy trial in France, see Cavazzana-Calvo et al. (2000) “Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease” Science Volume 288 p. 669–672.)