The compelling simplicity of gene therapy attracts great attention, with interest swinging between enthusiastic optimism when there is dramatic progress and scathing criticism when things go badly. Calling it "gene therapy" does imply the approach will work (it's written on the tin), but it has been a long and difficult road towards success.
The University College London/Moorfields study is a welcome step forward. It highlights the principle that gene therapy can be used to improve vision in some patients with Leber's congenital amaurosis, giving hope where there was none before. Hope is contagious and many people with incurable genetic diseases will be interested in these findings, hoping that gene therapy treatments may soon be found for them. Gene therapy can work, but only when the healthy "transgenes" can be introduced efficiently into diseased cells. The biggest step in turning principle into practice occurred when scientists appreciated the need to prioritise efficient "transgene delivery". In the case of the Moorfields study, the transgenes are delivered using a vector – a harmless virus that "infects" the diseased cells – injected directly under the retina.
Similar effects have been seen once before, at Great Ormond Street Hospital, in the treatment of children with severe combined immune deficiency (SCID); the "bubble boys". There, vectors were administered to bone marrow stem cells isolated from patients, and then reintroduced so that they can repopulate the patients' immune systems with healthy cells.
In all cases, it's about efficient transgene delivery, and we anticipate continued success in other areas where diseased target cells can be accessed directly – for example by injection in the treatment of Parkinson's disease, or by treatment of stem cells in other immune disorders.
Although animal research is essential for most forms of medicine, clinical trials are particularly important to assess strengths and weaknesses of complex approaches like gene therapy. For example, the toxicities seen in four patients with SCID (where the transgene became inserted into the patients' chromosomal DNA and caused leukaemia) were not anticipated from preclinical studies. Only because some patients were enrolled in experimental trials have we now learnt the importance of making safer vectors for SCID, and future trials will be conducted using these new vectors. SCID is a life-threatening disease, and for patients without bone marrow donors, gene therapy now provides a remarkable, potentially curative, way forward.
Applying gene therapy to diseases where target cells are spread around the body, for example in cancer, requires development of more sophisticated vectors that can be injected into the patients' bloodstreams and can seek out and deliver therapeutic transgenes selectively to the target diseased cells. That is the area where much of gene therapy research is now focused, and progress in delivery will undoubtedly lead to even more exciting breakthroughs, including in the treatment of some of the major killers of our time – cancer and heart disease.
Len Seymour is professor of gene therapies at Oxford University and president of the British Society for Gene Therapy