Adenosine deaminase deficiency as the first target disorder in gene therapy

In the past decade, the advent of gene therapy has been acclaimed as a revo lutionary medical intervention, embraced with great enthusiasm. However, re cent disappointing results of the considerable clinical trials have also cl early demonstrated that such an initial expectation was an overestimation o f gene therapy. There are only a few successful cases despite the 3000 pati ents who have been treated with various forms of gene therapy. Gene therapy for severe combined immunodeficiency (SCID) caused by adenosine deaminase (ADA) deficiency is one of the few such cases where results have been promi sing. In particular, peripheral T-lymphocytes-directed gene therapy provide s further immunological improvements for patients with ADA-SCID receiving t he PEG-ADA treatment whereas gene therapy targeting haematopoietic stem cel l has so far proved insufficient for clinical benefits. This report will re view crucial problems elucidated in the past five clinical trials for ADA-S CID and gives an outline of the next generation of stem cell gene therapy i n Japan.