Gene Therapy for Sickle Cell Anemia

Overseen By Emily Morris

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Daniel Bauer

Disqualifiers: Uncontrolled infection, Active malignancy, Major surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy for sickle cell disease and transfusion-dependent beta-thalassemia. The treatment, Hematopoietic Stem Cell BCL11A Enhancer Gene Editing, edits the patient's own blood stem cells to increase healthy hemoglobin and reduce sickle hemoglobin, potentially curing these conditions. This approach resembles a bone marrow transplant but uses the patient's own cells, reducing risks like rejection. Suitable candidates have sickle cell disease with frequent severe pain or transfusion-dependent beta-thalassemia. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol specifies that if you are taking hydroxyurea, you should stop it when transfusions prior to gene therapy begin. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that a new gene editing technique targeting the BCL11A enhancer is promising for treating sickle cell anemia. In one study, 86% of patients had their bone marrow cells successfully edited six months after treatment. This led to at least 40% of their blood containing healthy fetal hemoglobin, which does not cause cells to sickle and benefits patients.

The treatment uses the patient's own stem cells, reducing the risk of complications like Graft-Versus-Host Disease, a common issue with donor cells. This method might also allow for less chemotherapy, potentially reducing side effects. While these results are encouraging, it is important to remember that this is still early research, and the full safety profile is under study.

Additionally, the FDA has approved similar gene therapies for sickle cell disease, indicating some confidence in the safety of gene-based treatments for this condition. However, each therapy differs, so ongoing trials will continue to evaluate their safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell anemia?

Researchers are excited about the Hematopoietic Stem Cell BCL11A Enhancer Gene Editing treatment because it offers a potentially curative approach for sickle cell anemia, unlike current treatments that mainly manage symptoms and complications. Most treatments for sickle cell anemia, like hydroxyurea or blood transfusions, focus on reducing pain crises and increasing red blood cell count temporarily. This gene therapy stands out by directly modifying the BCL11A gene enhancer, which could lead to the production of healthier red blood cells by reactivating fetal hemoglobin production. This approach targets the root cause of the disease, offering hope for a long-term solution rather than just short-term relief.

What evidence suggests that this gene therapy might be an effective treatment for sickle cell anemia?

Research has shown that gene therapy targeting the BCL11A gene could be a promising treatment for sickle cell anemia. Studies have demonstrated that this method increases the amount of fetal hemoglobin, a healthy type of hemoglobin, in patients. Specifically, one study found that 86% of blood stem cells were successfully edited, resulting in at least 40% fetal hemoglobin in patients after six months. The therapy activates fetal hemoglobin, which helps prevent red blood cells from sickling. This approach uses the patient's own cells, reducing the risk of complications often seen with traditional transplants. Overall, these findings suggest that this gene-editing therapy could be a powerful treatment option for sickle cell anemia. Participants in this trial will receive the Hematopoietic Stem Cell BCL11A Enhancer Gene Editing treatment to evaluate its effectiveness and safety. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with severe beta-thalassemia or sickle cell disease. Candidates must have a specific genetic variant (rs114518452). They should be eligible for bone marrow transplant but will use their own modified cells to avoid complications like GVHD.

Inclusion Criteria

I am between 13 and 40 years old.

My condition is considered severe by my doctor.

I have been diagnosed with sickle cell or β-thalassemia through genetic testing.

Exclusion Criteria

I have not had major surgery in the last 30 days.

I cannot take busulfan due to health reasons.

I have a high level of iron in my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Patients with SCD receive blood transfusions for 3 months prior to stem cell collection

12 weeks

Stem Cell Collection and Gene Editing

Peripheral stem cell mobilization and collection by apheresis, followed by gene editing

2-4 weeks

Conditioning and Infusion

Myeloablative conditioning with busulfan followed by infusion of gene-edited cells

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Hematopoietic Stem Cell BCL11A Enhancer Gene Editing

Trial Overview The trial tests gene editing on the patient's own blood stem cells, aiming to increase fetal hemoglobin production which could cure the disease. It involves modifying genes using Cas9 and then reintroducing these cells after chemotherapy.

How Is the Trial Designed?

Group I: Sickle Cell Disease and Transfusion-Dependent Beta-Thalassemia Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Daniel Bauer

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

The BCH-BB694 lentiviral vector effectively reactivates fetal hemoglobin production while reducing harmful adult sickle hemoglobin in sickle cell disease, showing a 3- to 5-fold increase in fetal hemoglobin levels in transduced cells.

Preclinical studies indicate that BCH-BB694 is non-toxic and can be produced at a clinically relevant scale, supporting its potential for safe and effective use in human trials for treating sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy. Brendel, C., Negre, O., Rothe, M., et al.[2020]

Targeted genome editing using CRISPR/Cas9 and TALENs can successfully correct the sickle cell mutation in the β-globin gene in hematopoietic stem cells, leading to the production of normal hemoglobin.

In laboratory tests, over 18% of CD34+ cells showed successful gene modification, indicating the potential for effective treatment of sickle cell disease in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRISPR/Cas9-Mediated Correction of the Sickle Mutation in Human CD34+ cells. Hoban, MD., Lumaquin, D., Kuo, CY., et al.[2022]

A novel gene-editing approach using electroporation achieved significant correction of the sickle cell mutation in hematopoietic stem cells, with about 30% correction at the DNA level and 80% at the protein level, demonstrating its potential efficacy for treating sickle cell disease.

The study showed that gene-edited CD34+ cells could successfully engraft and function in both mouse models and rhesus macaques for up to 12 months, indicating the long-term viability of this gene correction strategy for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation for engraftment of CD34+ cells gene-edited at the sickle cell disease locus in xenograft mouse and non-human primate models. Uchida, N., Li, L., Nassehi, T., et al.[2022]

Combining CRISPR-Cas9 editing of the BCL11A enhancers significantly enhances fetal hemoglobin (HbF) induction, which is crucial for treating β-hemoglobinopathies like sickle cell disease, as shown in patient-derived xenografts.

Editing hematopoietic stem and progenitor cells (HSPCs) without prior cytokine culture reduces the risk of unintended genetic damage while maintaining effective gene editing, suggesting a safer approach for potential in vivo therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells. Zeng, J., Nguyen, MA., Liu, P., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12445678/

Hematopoietic stem cell therapy with gene modification to ... The gene-editing trial in SCD resulted in 86% editing in BM CD34+ cells 6 months post-gene-editing therapy, at least 40% HbF during the follow- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06647979

Hematopoietic Stem Cell BCL11A Enhancer Gene Editing ... This is a non-randomized, single center, open-label, pilot safety and feasibility study involving a single infusion of autologous bone marrow derived CD34+ ...

3. stjude.org stjude.org/media-resources/news-releases/2025-medicine-science-news/gene-therapy-for-sickle-cell-and-beta-thalassemia-works-by-disrupting-three-dimensional-genome-structure.html

Gene therapy for sickle cell and β-thalassemia works by ... As a result, BCL11A is silenced, leading to reactivation of fetal hemoglobin, which compensates for defective adult hemoglobin in sickle cell ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2031054

CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β ... BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells. We performed electroporation of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666379125004495

Multiplex base editing of BCL11A regulatory elements to ... Base editing is effective in long-term repopulating HSPCs and results in robust HbF reactivation in vivo. These findings demonstrate that ...

6. fda.gov fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

FDA Approves First Gene Therapies to Treat Patients with ... The FDA approved the first cell-based gene therapies, Casgevy and Lyfgenia, for the treatment of sickle cell disease in patients 12 years ...

7. cell.com cell.com/cell-stem-cell/abstract/S1934-5909(24)00376-X

BCL11A +58/+55 enhancer-editing facilitates HSPC ... Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal ...