Gene Therapy for Sickle Cell Disease
(GRASP Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial aims to test a new gene therapy for people with sickle cell disease. The treatment involves altering a specific gene to increase a healthy form of hemoglobin, potentially reducing painful episodes and improving the condition. Participants will receive their own modified blood stem cells (autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a), which lowers the risk of complications compared to traditional methods. The study seeks individuals with sickle cell disease who have experienced at least four painful episodes in the past two years. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in sickle cell therapy.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients on a chronic transfusion regimen for stroke prevention are not eligible, which might imply some restrictions. It's best to discuss your specific medications with the trial team.
Is there any evidence suggesting that this treatment is likely to be safe for humans?
Research has shown that the gene therapy treatment being tested for sickle cell disease appears promising in terms of safety. In an initial trial with 10 patients, no unexpected safety problems occurred. Patients experienced an increase in fetal hemoglobin, a healthy type of hemoglobin that doesn't cause sickling, suggesting the treatment is well-tolerated.
The treatment uses a virus to add new genetic material to a patient’s own blood stem cells. Lab studies with mice and cells from sickle cell patients demonstrated that this method effectively reduces the amount of harmful sickle hemoglobin in red blood cells without causing serious side effects.
Overall, this gene therapy is considered safe based on the available studies. It aims to reduce complications from sickle cell disease by increasing healthy hemoglobin levels.12345Why do researchers think this study treatment might be promising for sickle cell disease?
Most treatments for sickle cell disease focus on managing symptoms or preventing complications, often using medications like hydroxyurea or blood transfusions. But this new gene therapy approach is different because it involves modifying a patient's own stem cells. Researchers are excited because this treatment uses a lentiviral vector to deliver a small hairpin RNA (shRNA) that targets and reduces the activity of the BCL11a gene. This mechanism is promising because it could potentially increase fetal hemoglobin production, which might reduce the sickling of red blood cells and offer a more lasting solution compared to current therapies.
What evidence suggests that this gene therapy could be an effective treatment for sickle cell disease?
Research has shown that gene therapy targeting the BCL11A gene can increase healthy hemoglobin levels in people with sickle cell disease. In studies, doctors used a special virus to modify this gene in patients' own blood stem cells, yielding promising results. This trial involves a single infusion of autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11A. This treatment reduces the harmful type of hemoglobin in red blood cells. A small trial with 10 patients found no unexpected safety issues and confirmed higher levels of healthy hemoglobin. This approach aims to reduce the painful episodes caused by sickle cell disease by increasing the amount of healthier hemoglobin in the blood.24678
Who Is on the Research Team?
David Williams
Principal Investigator
Boston Children's Hospital
Are You a Good Fit for This Trial?
This trial is for people aged 13-40 with severe sickle cell disease (HbSS or HbS/β0 thalassemia) who've had at least 4 pain crises in the last 2 years. They need good organ function, no matching bone marrow donor, and can't be on chronic blood transfusions or have a history of stroke, certain infections like HIV/Hepatitis, liver issues from iron overload, or other conditions that could interfere with treatment.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Pre-treatment
Patients receive blood transfusions for at least 3 months to achieve a HbS level ≤ 30% before stem cell collection
Stem Cell Collection and Transduction
Peripheral stem cell mobilization and collection by apheresis, followed by transduction with lentiviral vector
Conditioning and Infusion
Myeloablative conditioning with busulfan followed by infusion of transduced cells
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a
Find a Clinic Near You
Who Is Running the Clinical Trial?
David Williams
Lead Sponsor
Genetix Biotherapeutics Inc.
Industry Sponsor
California Institute for Regenerative Medicine (CIRM)
Collaborator
bluebird bio
Industry Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
Blood and Marrow Transplant Clinical Trials Network
Collaborator