This project involved the conduct of a clinical trial of gene therapy for the inherited deficiency of the phagocytic cell immune system known as chronic granulomatous disease (CGD). Patients with CGD have defective circulating blood neutrophils that fail to produce microbicidal hydrogen peroxide. They suffer from recurrent life threatening infections and premature mortality. This year we completed a phase I study of gene therapy for the p47phox deficient autosomal recessive form of CGD. In that study we demonstrated that a single cycle of gene therapy targeting cytokine mobilized and purified stem cells could result in production of small numbers (.004% to .05%) functionally corrected neutrophils in the peripheral blood that persisted for 2 to 6 months. This demonstrated that it is possible to provide partial and transient correction of the CGD defect in patients by gene therapy. While the level of correction is not a cure and may or may not provide clinical benefit, it represents a very important demonstration of the principle that gene therapy can correct the biochemical defect of CGD. It may be that even low level and transient correction might provide clinical benefit in the setting of severe recurrent infections. With that principle in mind, the basic scientific work was performed as part of project Z01-AI-00644-07 to develop the tools to achieve efficient gene transfer to stem cells for correction of the most common and severe form of CGD, gp91phox deficient X-linked CGD. This work has led to the initiated of a second phase of a clinical trial for the X-linked form of CGD that is ongoing. Patients targeted for gene therapy treatment are those with ongoing indoent life-threatening infection. In this setting new information about the science of gene therapy will be obtained while potentially augmenting patient host defense against the ongoing infection. Preliminary results in two patients demonstrate that gene therapy has resulted in more than 1 in 1000 circulating neutrophils being oxidase normal with the effect still see at over two months. In this new study up to six cycles of gene therapy will be given to each patient enrolled in the study.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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