Gene therapy is the delivery of genetic material to correct a genetic defect associated with severe disease, replacing a non-functional gene with a functional version or inactivating a malfunctioning gene. It is in a sense the ‘holy grail’ of genetic medicine, offering the potential of a genuine cure for serious inherited diseases, and potentially also more common conditions such as cancer. However, it is difficult to achieve long-term therapeutic effects, and there is a risk of cancers caused by inappropriate insertion of the gene therapy vector in the cellular genome of the patient.
One of the earliest gene therapy successes was for the X-linked form of severe combined immunodeficiency (SCID-X1); this is a rare disease where a mutation prevents the formation of a functional immune system. Affected children, if untreated, die very young from infections. Gene therapy trials produced very positive results (see previous news), but were dogged by cases of therapy-associated leukaemia (see previous news).
However, their immune systems were not perfect, being better able to generate T-cells than NK-cells, and some (but not all) needed additional therapy to provide antibodies, another crucial element of the immune system. More seriously, a total of four of the nine boys developed leukemia; they received chemotherapy, but one died. In the three survivors, normal immune functions returned once chemotherapy ended.
Comment: Gene therapy was not completely effective in one of the nine boys, and caused leukaemia in four others, in one case fatal. However, it is important to note that without treatment, all of these boys would have died much earlier. Even where tissue-matched bone marrow transplants (the only alternative treatment) are available, survival rates are reportedly only around 70%.
Clearly, gene therapy is a long way from being suitable for moderate conditions, or those where alternative treatments are possible, but for these most serious diseases, it can work. The ongoing challenge is to maximise efficacy whilst minimising the associated risks.