An interventional study of bone marrow aspiration and biopsy in Adenosine Deaminase Deficiency, sponsored by Istituto Giannina Gaslini. Completed at 1 site in Italy. Open to participants aged 1 Day to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-20.
Sponsored by Istituto Giannina Gaslini · Not applicable, Interventional, and Diagnostic
Adenosine deaminase 2 deficiency (DADA2), caused by autosomal recessive mutations in the ADA2 gene (OMIM: 607575), is an autoinflammatory disease characterized by early-onset inflammatory vasculopathy, stroke, and immunodeficiency (cytopenias and antibody deficiency). Due to its wide clinical variability and heterogeneous presentation, a large proportion of patients with DADA2 remain undiagnosed.
Anti-TNF therapy is effective in DADA2 patients with inflammatory vasculopathy; however, its long-term efficacy and safety remain unknown.
We propose to:
i) Improve the rate of DADA2 diagnosis in Italy and assess the long-term efficacy and safety of currently available treatments (anti-TNF agents, immunosuppressants, and hematopoietic stem cell transplantation [HSCT]);
ii) Further characterize patients with a predominantly hematological phenotype;
iii) Develop a gene therapy approach for patients with DADA2, based on the transfer of the functional ADA2 gene into cells.
Istituto Giannina Gaslini is the lead sponsor of 50 studies on the registry; 33 are open to participants now.
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Exclusion Criteria:
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Procedure: bone marrow aspiration and biopsy
Bone marrow biopsy for morphological examination to quantify overall hematopoietic cellularity, the relative frequencies of individual hematopoietic lineages, lymphocytic infiltration, and fibrosis.dergo bone marrow aspiration and bone marrow biopsy
Increase the number of DADA2 diagnoses
Increase the rate of DADA2 diagnosis through the development of a new enzymatic assay to measure ADA2 activity in dried plasma spots on filter paper and by providing access to molecular testing for patients with suspected DADA2. We will also establish an Italian cohort of patients with DADA2 through the already established Eurofever registry.
Time frame: Month 36
Functional and phenotypic characterization of the bone marrow in patients with DADA2 and preclinical studies for gene therapy.
The pathogenesis of hematological manifestations in DADA2 remains largely unknown. Possible mechanisms include an intrinsic defect in ADA2 in bone marrow (BM) progenitor cells or an environmental effect mediated by pro-inflammatory cytokines, as suggested by the strong interferon signature observed in patients with DADA2. The efficacy of anti-TNF treatment in these patients remains controversial, as both treatment-responsive and treatment-refractory cases have been reported, with some patients requiring hematopoietic stem cell transplantation (HSCT). It is therefore clinically relevant to investigate the potential roles of type I interferon and TNF in the development of hematological manifestations of DADA2 and to determine whether their effects occur at earlier or later stages of bone marrow damage. This could influence therapeutic decision-making by establishing whether early TNF inhibitor treatment provides a clinical benefit or slows the progression of hematological
Time frame: Month 36
Develop a Gene Therapy Approach for DADA2
The development of a gene therapy approach for autologous stem cell transplantation may offer a curative treatment for DADA2. Alternative therapeutic strategies are needed to avoid potential transplant-related complications, such as graft-versus-host disease (GVHD) and veno-occlusive disease. There is a strong rationale for developing an approach based on the genetic correction of patients' hematopoietic stem and progenitor cells. Gene therapy for ADA1 deficiency, a form of severe combined immunodeficiency (SCID), has demonstrated safety and efficacy in clinical trials conducted by Unit 2 . Furthermore, studies conducted by Unit 2 and other research groups have shown that gene therapy based on the ex vivo transduction of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) using lentiviral vectors (LVs) can provide stable, long-term gene expression, even in slowly dividing cells that are difficult to transduce, including long-term repopulating hematopoietic stem ce
Time frame: Month 36
Plan to share: No
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is completed, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Severe combined immunodeficiency due to adenosine deaminase deficiency
Istituto Giannina Gaslini