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BioDrugs

, Volume 16, Issue 4, pp 229–239 | Cite as

Gene Therapy in Infants with Severe Combined Immunodeficiency

  • Makoto Otsu
  • Fabio Candotti
Gene Therapy

Abstract

Severe combined immunodeficiencies (SCID) are rare disorders that represent paediatric medical emergencies, as the outcome for affected patients can easily be fatal unless proper treatment is performed. The only curative treatment for SCID is reconstitution of the patient’s immunity. For more than 30 years, allogeneic bone marrow transplantation (BMT) has been extremely successful for SCID. However, BMT often results in only incomplete restoration of B cell function in treated patients, especially when haploidentical donors are used. In addition, BMT can be associated with severe complications such as graft-versus-host disease (GVHD). Alternative forms of therapy for SCID are therefore desirable. Genetic correction of peripheral T lymphocytes and/or haematopoietic stem cells (HSCs) by retrovirally mediated gene transfer has been attempted for patients with SCID due to adenosine deaminase deficiency, the first genetic disease targeted in clinical gene therapy trials with very limited success, overall. After these pioneer trials, recent progress has led to significant improvement of gene transfer techniques and better understanding of HSC biology which has culminated in the recent success of a gene therapy trial for patients affected with X-linked SCID (X-SCID). In this trial, patients with X-SCID received autologous bone marrow stem/progenitor cells which had been retrovirally transduced with a therapeutic gene. Based on the current follow-up, the overall efficacy of this gene therapy procedure is to be considered similar to or even better than that achievable by allogeneic BMT, because patients were not exposed to the risks of GVHD. Although these exciting results have clearly demonstrated that gene therapy is a feasible therapeutic option for X-SCID, they have also raised important questions regarding the long-term outcome of this experimental procedure and the possibility of translating this success into applications for other forms of SCID.

Keywords

Gene Therapy Bone Marrow Transplantation Allogeneic Bone Marrow Transplantation Severe Combine Immunodeficiency Gene Therapy Trial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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© Adis International Limited 2002

Authors and Affiliations

  1. 1.Genetics and Molecular Biology BranchNational Human Genome Research Institute, National Institutes of HealthBethesdaUSA

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