Gene Editing Treatment Using BCL11A Enhancer for Severe Beta-Hemoglobin Disorders Including Sickle Cell Disease and Beta-Thalassemia in Patients Aged 13 to 40

What this Trial Is About

This research aims to evaluate gene therapy using gene editing for severe beta-hemoglobinopathies like sickle cell disease and transfusion-dependent beta-thalassemia. The study focuses on introducing new genetic material into a patients own blood stem cells to fix or replace defective genes, potentially increasing healthy fetal hemoglobin and reducing sickle hemoglobin. This trial is a phase 1 pilot safety and feasibility study led by Daniel Bauer to explore this innovative treatment approach. Participants will receive a single infusion of their own bone marrow-derived CD34 blood stem cells that have been edited targeting the BCL11A gene enhancer using a specialized Cas9 gene editing tool. Before infusion, patients undergo chemotherapy conditioning with busulfan to prepare the body. Stem cells are collected by apheresis after mobilization, with some reserved as backup. The study enrolls subjects aged 13 to 40 years with sickle cell disease or beta-thalassemia, grouped by age strata and diagnosis. During the 24-month follow-up, participants will have regular assessments including blood counts, hemoglobin levels, and monitoring for sickle cell complications like acute chest syndrome and stroke. Quality of life and safety outcomes such as serious adverse events and malignancies will also be tracked. The primary outcome is engraftment of the gene-edited cells by 42 days post-infusion. Continuous monitoring ensures participant safety and collects data on treatment impact over time.

Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe β-Hemoglobinopathies