Clinical Research Directory

Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy

Background: X-linked severe combined immunodeficiency (XSCID) is a rare inherited disorder that affects the immune system. It is caused by a change in the IL2RG gene. Researchers are investigating a new type of gene therapy for people with XSCID. This technique, called base-edited stem cell transplants, involves collecting a person s own stem cells, editing the genes to repair IL2RG gene, and returning the edited cells to the person. Objective: To test base-edited stem cell transplants in people with XSCID. Eligibility: People aged 3 years and older with XSCID. Design: Participants will be screened. They will have a physical exam. They may give blood, urine, and stool samples. They may have tests of their heart and lung function. They may have fluid and cells drawn from their bone marrow. Participants will undergo apheresis. Blood will be taken from the body through a needle inserted into 1 arm. The blood will pass through a machine that separates out the stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will undergo gene editing. Participants will be admitted to the hospital 1 week before treatment. They will receive a central line: A flexible tube will be inserted into a large vein. This tube will be used to administer drugs and draw blood during their stay. They will receive drugs to prepare their bodies for the treatment. The base-edited stem cells will be infused through the central line. Participants will remain in the hospital for at least 3 weeks while they recover. Follow-up visits will continue for 15 years.

Natural History Study of SCID Disorders

This study is a prospective evaluation of children with Severe Combined Immune Deficiency (SCID) who are treated under a variety of protocols used by participating institutions. In order to determine the patient, recipient and transplant-related variables that are most important in determining outcome, study investigators will uniformly collect pre-, post- and peri-transplant (or other treatment) information on all children enrolled into this study. Children will be divided into three strata: * Stratum A: Typical SCID with virtual absence of autologous T cells and poor T cell function * Stratum B: Atypical SCID (leaky SCID, Omenn syndrome and reticular dysgenesis with limited T cell diversity or number and reduced function), and * Stratum C: ADA deficient SCID and XSCID patients receiving alternative therapy including PEG-ADA ERT or gene therapy. Each Group/Cohort Stratum will be analyzed separately.