The long term results of gene therapy for severe combined immunodeficiency (SCID) – a fatal disorder of purin metabolism and immunodeficiency that is caused by the lack of Adenosine Deaminase (ADA) was the background of this research’s journal. The researchers infused autologus CD34+ bone marrow cells transduced with retroviral vector containing the ADA gene into object who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan as their methods.
A fatal autosomal recessive form of severe combined immunodeficiency (SCID) used to know as Adenosine Deaminase (ADA) deficiency. This conditition characterized failure to thrive and impaired immunoresponses which may lead to reccurent infections. It also influenced purine metabolism into toxic levels that can cause hepatic, skeletal, neurologic, behavioral alterations, and sensorineural deafness. Many therapies of this condition has a lot of limitation from only available for a minority patients, high risk of death or lack of engraftment,fail to sustain correction of immunodeficiency until the high cost of lifelong therapy.
Major experiments have shown the effectiveness and safety of gene therapy in patients with SCID which is caused by ADA deficiency. In this trial, before gene therapy, a central venous catheter was implanted and bone marrow specimens were obtained and cryopreserved for later usage possibilities. Then, gene therapy consisted of the infusion of CD34+ marrow cells that had been transduced with the ADA-containing vector is administered.
The presence of ADA was recorded through detection of its enzymatic activity in blood mononuclear cells, marrow mononuclear cells, T cells, and red cells and was confirmed through flow cytometry of T and B cells. The ADA activity in blood mononuclear cells and red cells was significantly higher at 1 year than at baseline. The activity in white cells and red cells resulted in a significant reduction of toxic levels of purine metabolites in red cells at 1 year.
A progressive increase of T-cell counts was confirmed after administration of ADA vector. The natural killer cell’s level were significantly increase at 3 years and showed normal cytotoxic activity against K 562 cells. Proliferalitive responses of T-cells agains mitogens were normal by 6 to 12 months of follow-up in all patients and remained normal during follow-up period. Like T-cell, B cell also increased progessively after this gene therapy. The level of IgA and IgM reached normal values in major patients.
This treatment of gene therapy supplies patients with hematopoetic stem cells that pass a functional ADA gene to all progeny, and there was an improvement of immune function and protection against severe infection. The continuous expression of ADA in multiple hematopoetic-cell lineages allowed for the detoxification of purine metabolites and improvement in patient’s physical development.
As conclusion, this study suggests that gene therapy in combination with nonmyeloablative conditioning may be an option to be administered for patients with SCID due to ADA deficiency who lack an HLA-identical sibling donor and could be successfully extended to the treatment of other congenital disease which involving hemapoetic system.
I got this medical journal at The New England Journal of Medicine Volume 360:447-458, you may read a Full Text article or you can also download in PDF Format. Thank You.
