What is the role of gene therapy in the treatment of severe combined immunodeficiency (SCID)?

Updated: May 27, 2020
  • Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Despite the success that has been seen in some SCID patients treated with bone marrow transplantation, other patients experince failure to restore B-cell function or failure or rejection of the graft over time. A novel alternative strategy to circumvent graft failure/rejection is the use of gene transfer into autologous stem cells using retroviruses.

Gene therapy is a viable therapeutic option; advances in biotechnology have enabled the performance of this highly complex treatment for several immunodeficiency syndromes. [26]

Cavazzana-Calvo et al published reports of the successful results of gene therapy for SCID-X1 disease in 2 children, opening new horizons for the future of these patients. [5]  This therapy resulted in complete immune reconstitution of the lymphoid system, with T-, B-, and NK-cell counts comparable to age-matched controls. [5]  An update on these 2 patients by the same authors and a report on 3 others confirmed the previous results.

Patients with ADA deficiency were the first to be enrolled in gene therapy trials. Since 2000, over 100  patients with ADA-SCID have been treated with gamma-retrovirus or lentivirus-mediated autologous hematopoietic stem cell gene therapy (HSC-GT), and the excellent safety and efficacy observed in these cases has established HSC-GT as an equal alternative to HSCT for these patients. [28]

In addition to ADA deficiency, , SCID-X1, WAS, RAG1 deficiency, and CD3 deficiency have been successfully treated with gene-modified autologous HSC-GT. In this technique, RNA viruses are the vectors most commonly used to introduce genetic information into hematopoietic stem cells and/or progenitor cells. It has been demonstrated that several T-cell precursors that carry a wild-type sequence of the disease-causing gene or a less harmful mutation can mature into functional mature T cells that provide adequate immunity. 


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