what research has been conducted about scid

What research has been conducted about scid trial#
What research has been conducted about scid series#

For ADA-SCID, more than 40 patients have been treated worldwide with 100% survival and an overall efficacy, as determined by cessation of ERT, of more than 70%. One important feature is the safety profile associated with these studies.

Clearly there is a need to validate these findings in the clinical setting. These are important data especially because, as the authors state, the use of ERT for a short time period after gene therapy may not only protect patients in the period of lymphopaenia after chemotherapy, but may also promote engraftment of gene-corrected cells. The reasons for this are not clear but may relate to the role of exogenous ADA in detoxifying the marrow or thymic stromal microenvironment, thereby permitting the engraftment and survival of gene-modified cells. In this setting, they found that in contrast to mice that had stopped ERT, mice receiving ERT for 1 or 4 months after gene transfer had significantly increased levels of gene-modified cells in the thymus.

However, the most striking results were seen in experiments that most accurately represent the clinical scenario, which is the use of gene-modified lin-ve progenitor cells in nonmyeloablated (200 cGy) hosts. The first finding was that continued use of ERT did not blunt gene-modified cell engraftment.

What research has been conducted about scid series#

To address this formally, Carbonaro et al performed a series of experiments in which ERT was continued for either 1 or 4 months after gene transfer. Contrasting anecdotal clinical data are available, with one report suggesting that ERT cessation allowed gene-modified cell development 9 whereas others, 8 including the present Candotti et al report, show that ERT usage may actually promote gene-modified cell proliferation. The other major issue in the implementation of clinical gene therapy trials has been whether the use of ERT promotes or negates the engraftment of gene-modified cells. Importantly, because the same vectors and transduction protocols were used in the 2 phases of the study, a direct comparison could be made and demonstrates that conditioning is required for gene-modified cell engraftment. In 6 patients treated in the second phase, 3 were able to stop ERT long term and had significant engraftment of gene-corrected cells in the periphery with sustained immune recovery.

What research has been conducted about scid trial#

After reports emerging from successful studies in Europe, the trial protocol was amended to include a low dose of intravenous busulphan (65-90 mg/m 2) and cessation of ERT.

In these 4 individuals, minimal or no engraftment of gene-modified cells was seen. 2 In the first phase, for safety reasons, patients were treated without cytoreductive conditioning and with ongoing ERT. In their report, Candotti et al describe 10 patients treated in 2 different phases of the same trial. However, in both studies, no comparative group was available to determine the absolute need for conditioning. 7, 8 In both cases, the use of chemotherapy (either busulfan 4 mg/kg or melphalan 140 mg/kg) was thought to remove autologous ADA-deficient HSCs and thereby promote the engraftment of gene-modified cells. Two clinical studies have shown the long-term success of hematopoietic autologous stem cell (HSC) gene therapy in correction of ADA-SCID.