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Severe Combined Immune Deficiency

Gene Therapy

Understanding the genes responsible for SCID has also led to an increased understanding of the genes involved in the overall development of the immune system. It has also helped to unravel the complicated signaling pathways between the cells of the immune system that control and define the immune response itself. There has also been another major benefit. The study of SCID has, in the past, aided in developing an effective program for bone marrow transplantation.

Interleukin binds to its two-part receptor, triggering JAK-1 and JAK-3 to add phosphates to each other and to STAT (signal transducers and activators of transcription). This allows the STATs to combine and enter the nucleus, where they promote gene expression leading to immune system development. SCID can arise from mutations that inactivate either the γ subunit or JAK-3 (shaded structures).

In 1990 the first gene therapy was attempted in two ADA-SCID patients. ADA-SCID was specifically chosen for the first attempted gene therapy for several reasons: bone marrow transplantation had indicated that replacing the defective gene was possible; mouse SCID models had been effectively treated through gene therapy; and ADA-SCID could be treated with some success with enzyme-replacement therapy, enhancing the opportunity for successful gene therapy.

Unfortunately, the majority of ADA-SCID patients, as well as the 3,000 patients enrolled in gene therapy trials for a broad array of other diseases since the first ADA-SCID gene therapy, have not been significantly helped. One exception is the very first gene therapy patient, four-year-old Ashanti de Silva who, ten years later, had a normal lifestyle, with a level of 20 to 25 percent normal T-lymphocytes. Learning from these gene therapy experiences, French researchers modified the procedure. In 2000 they reported successful gene therapy for two infants with SCID-X1. The patients had left the hospital and its protective isolation after a three-month stay. Ten months after gene therapy, they remained healthy, with normal levels of B- and T-lymphocytes and natural killer cells. Thus SCID continues to define the current state of the art for gene therapy, exposing its limitations while simultaneously pointing to its eventual success.

Diane C. Rein

Bibliography

Fischer, Alain. "Primary Immunodeficiency Diseases: An Experimental Model for Molecular Medicine." Lancet 357, no. 9271 (2001): 1863-1869.

Fischer, Alain, et al. "Gene Therapy for Human Severe Combined Immunodeficiencies." Immunity 15 (2001): 1-4.

Leonard, Warren J. "X-linked Severe Combined Immunodeficiency: From Molecular Cause to Gene Therapy within Seven Years." Molecular Medicine Today 6, no. 10 (2000): 403-407.

Wheelwright, J. "Body, Cure Thyself." Discover 23, no. 2 (2002): 62-68.

Additional topics

Medicine EncyclopediaGenetics in Medicine - Part 4Severe Combined Immune Deficiency - Types And Severity Of Immunodeficiency Diseases, Scid, Gene Therapy