Trial reportThe Journal of clinical investigation2017
Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.
Trial report in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00794508 (MND-ADA Transduction of CD34+ Cells From the Bone Marrow Of Children With Adenosine Deaminase), which is not on this map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
MND-ADA Transduction of CD34+ Cells From the Bone Marrow Of Children With Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID): Effect of Discontinuation of PEG-ADA and Marrow Cytoreduction With Busulfan
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.Nature communications · 2022Pooled it
- Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency.Blood · 2021Trial
- Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.Blood · 2017Trial
- Stem cell-based therapies in pediatric disorders: translational advances, unresolved challenges, and future horizons.Stem cell research & therapy · 2026Review
- Gene therapy for inborn errors of immunity: past progress, current status and future directions.Rare disease and orphan drugs journal · 2025Article
- Viral-based gene therapy clinical trials for immune deficiencies and blood disorders from 2013 until 2023 - an overview.Regenerative therapy · 2025Review
- A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.Nature communications · 2024Article
- Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency.Journal of clinical immunology · 2024Article
- Hemorrhage of Upper Digestive and Respiratory Tracts in a Child with Glanzmann Thrombasthenia.Maedica · 2023Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- Living Biomaterials to Engineer Hematopoietic Stem Cell Niches.Advanced healthcare materials · 2022Article
- Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience.Journal of clinical immunology · 2022Article
- Nonconditioned ADA-SCID gene therapy reveals ADA requirement in the hematopoietic system and clonal dominance of vector-marked clones.Molecular therapy. Methods & clinical development · 2021Article
- Recent advances in lentiviral vectors for gene therapy.Science China. Life sciences · 2021Review
- Built to last: gene therapy for ADA SCID.Blood · 2021Article
- Normal IgH Repertoire Diversity in an Infant with ADA Deficiency After Gene Therapy.Journal of clinical immunology · 2021Article
- Newborn Screening for Severe Combined Immunodeficiency: 10-Year Experience at a Single Referral Center (2009-2018).Journal of clinical immunology · 2021Article
- Gene therapy using haematopoietic stem and progenitor cells.Nature reviews. Genetics · 2021Review
- Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Hematopoietic Tumors in a Mouse Model of X-linked Chronic Granulomatous Disease after Lentiviral Vector-Mediated Gene Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
Corrections and comments
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Authors and funding
44 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundAutologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study.
methodsTen subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution.
resultsWith the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1-2.6) and granulocytes (VCN = 0.01-0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant.
conclusionThese results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile.
trial registrationClinicalTrials.gov NCT00794508.
fundingFood and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA Clinical and Translational Science Institute awards, UL1RR033176 and UL1TR000124.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.