Gene Therapy for Bubble Boy Disease

Overseen By Suk S De Ravin, M.D.

Age: Any Age

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Intravenous gamma globulin

Disqualifiers: HLA-matched sibling, Hypersensitivity to busulfan, Childhood malignancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for individuals with X-linked severe combined immunodeficiency (XSCID), a rare genetic disorder that weakens the immune system. The treatment involves collecting a person's own stem cells, correcting the faulty gene, and returning the edited cells to strengthen the immune system. This trial is for individuals aged 3 years and older who have XSCID and meet specific health criteria, such as frequent infections or poor growth. Participants will stay in the hospital during the treatment and undergo follow-ups for many years to monitor the therapy's long-term effects. As a Phase 1/Phase 2 trial, it aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get a clear answer.

What prior data suggests that this gene therapy technique is safe for people with XSCID?

Research has shown that stem cell transplants using base editing are generally well-tolerated by people with X-linked severe combined immunodeficiency (XSCID). This treatment repairs the faulty IL2RG gene in a person’s own stem cells, helping to restore their immune system.

While specific side effects of this treatment remain limited, similar gene therapies have been found safe for related conditions. Previous gene therapy treatments for immune deficiencies have mostly been safe, with no major safety issues reported.

As this is an early-stage phase 1/2 trial, researchers are closely monitoring for any side effects. Participants will receive close medical supervision, particularly during their hospital recovery, to quickly identify and manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for Bubble Boy Disease, which often rely on bone marrow transplants or enzyme replacement therapies, this gene therapy uses base-edited hematopoietic stem and progenitor cells. This approach is unique because it directly targets and corrects the genetic defect at the root of the condition, potentially offering a more permanent solution. Researchers are excited because this method could significantly reduce the risk of complications and provide a long-lasting cure, rather than just managing symptoms. Additionally, this precise genetic editing aims to minimize off-target effects, making it a safer option for patients.

What evidence suggests that this gene therapy might be an effective treatment for XSCID?

Research shows that a new type of stem cell transplant, which participants in this trial will receive, could be a promising treatment for X-linked severe combined immunodeficiency (XSCID), also known as Bubble Boy Disease. This method repairs the faulty IL2RG gene in a person's own stem cells. Studies have found that similar gene therapy techniques have successfully restored immune function in patients with severe immune deficiencies. Specifically, infants with Bubble Boy Disease have been cured using this type of gene therapy. Base editing, a part of this process, reduces unwanted genetic changes while maintaining treatment effectiveness. Overall, this approach offers hope for a lasting solution for those affected by this rare immune disorder. ^{2 3 4 6 7}

Who Is on the Research Team?

Suk S De Ravin, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for people aged 3 years and older with X-linked severe combined immunodeficiency (XSCID), also known as 'Bubble Boy Disease'. Participants will undergo various screenings including physical exams, blood tests, and heart and lung function tests. They must be able to endure apheresis (a procedure to collect stem cells) and hospitalization.

Inclusion Criteria

I have a chronic lung condition confirmed by tests.

I have had long-term yeast infections in my mouth, throat, skin folds, or nails confirmed by lab tests.

Expected survival of at least 120 days

Exclusion Criteria

I cannot take busulfan due to health reasons.

Known hypersensitivity to busulfan or any component of the product

Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the participant, or would preclude the patient from successful study completion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Apheresis and Gene Editing

Participants undergo apheresis to collect stem cells, which are then gene-edited to repair the IL2RG gene

1 week

1 visit (in-person)

Treatment

Base-edited stem cells are infused through a central line; participants remain in the hospital for recovery

3 weeks

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Base-edited hematopoietic stem and progenitor cells

Trial Overview The trial is testing a new gene therapy for XSCID by editing the genes in a patient's own stem cells to repair the IL2RG gene defect. The process includes collecting stem cells through apheresis, gene editing in the lab, then infusing these edited cells back into patients after pre-treatment with drugs like Plerixafor, Filgrastim, Palifermin, Busulfan.

How Is the Trial Designed?

Group I: Single Arm Study Experimental Treatment 5 Interventions

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

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]

Hematopoietic stem cell gene therapy (HSCGT) using a lentiviral vector for the SGSH gene shows promise for treating Mucopolysaccharidosis type IIIA (MPSIIIA), with pre-clinical studies indicating effective gene transfer and safety in humanized mouse models.

The therapy demonstrated effective engraftment and biodistribution without vector shedding or germline transmission, and showed low genotoxicity, suggesting it is a safe and viable option for clinical trials in treating this neurological disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex Vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA. Ellison, SM., Liao, A., Wood, S., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38532630/

Restoring T and B cell generation in X-linked severe ... Base editing of hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematologic diseases.

2. withpower.com withpower.com/trial/phase-2-immunologic-deficiency-syndromes-2-2025-666ef

Gene Therapy for Bubble Boy Disease · Info for Participants Editing hematopoietic stem and progenitor cells (HSPCs) without prior cytokine culture reduces the risk of unintended genetic damage while maintaining effective ...

3. synthego.com synthego.com/blog/gene-therapy-cures-scid/

Gene Therapy Cures Infants with “Bubble Boy" Disease New gene therapy successfully cured infants suffering from “bubble boy" disease, a life-threatening disease that affects immune cell ...

4. nature.com nature.com/articles/d41587-019-00015-6

'Bubble boy' gene therapy reignites commercial interest Industry interest reignited by increased safety and efficacy of lentiviral gene therapies in several severe combined immune deficiencies.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11184316/

Restoring T and B cell generation in X-linked severe ... Taken together, these data suggest that autologous ex vivo base editing and HSC transplantation are potentially effective treatments for SCID-X1. However, gene- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06851767?term=%22gene+therapy%22+OR+%22gene+transfer%22+OR+%22virus+delivery%22

Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked ... This is a phase 1/2, non-randomized study of a single infusion of autologous hematopoietic stem/progenitor cells base-edited to repair interleukin 2 receptor ...

7. healio.com healio.com/news/hematology-oncology/20151205/gene-therapy-shows-promise-for-patients-with-chronic-scid-x1

Gene therapy shows promise for patients with chronic ... These data suggest that gene therapy may serve as salvage treatment for older patients with X-linked severe combined immunodeficiency, or SCID- ...