Base Editing Hematopoietic Stem Cell and BE T Cell Gene Therapy for CD40L-HyperIgM Syndrome-Single Patient Study
Background: X-linked hyper-IgM (HIGM) syndrome is caused by a mutation in the CD40 ligand (CD40L) gene. People with this disease have white blood cells that do not work properly. These people are at risk of severe infections and autoimmune diseases. Researchers want to know if these base-edited stem cells and T cells can help people with CD40L-HIGM syndrome.
Objective: To test base-edited stem cells and base-edited T cells in 1 person with CD40L-HIGM syndrome.
Eligibility: A single male with CD40L-HIGM syndrome.
Design: A single participant is planned to receive a single dose of edited stem cells and supportive treatment with edited T cells. Participant stem and T cells will undergo base editing to repair the mutation. In preparation for the gene therapy, the participant will receive busulfan chemotherapy and alemtuzumab. After treatment, the participant will have follow-up visits every few months in the first 2 years after treatment. Long-term visits will continue annually for 15 years.
⁃ This study is a single participant research study and to receive the study product, he needs to meet the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Has CD40L Q220X mutation
• Defective class switching
• Liver abnormalities (transaminases\>UL)
• Portal hypertension
• Consensus from Hepatology Consult to receive myeloid conditioning
• Ability to take oral medication and be willing to adhere to the intervention regimen
• Use of condoms or other methods to ensure effective contraception with partner
• Ability of subject to understand and the willingness to sign a written informed consent document