DeCure for Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSevere combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency maps to a 4-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-negative, due to adenosine deaminase deficiency is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
adenosine deaminase (ADA) — ADA is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 2r,3s,5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3IAR · 1.52 Å · ligand (2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-tetrahydro-2-(hydroxymethyl)furan-3-ol (3D1). Experimental structure, not a prediction.
What the evidence adds up to
Adenosine deaminase deficiency is an autosomal recessive metabolic disorder that causes severe combined immunodeficiency. In two kindreds studied in 1975, three infants had no detectable erythrocyte adenosine deaminase, and eleven first-degree relatives were heterozygous. Successful bone-marrow transplantation in two of those infants established normal humoral and cellular immunity, but the enzyme deficiency persisted in their erythrocytes. The enzyme deficiency did not impair the establishment of normal immune function by transplants from siblings who were either normal or heterozygous for the deficiency.
Complete deficiency of adenosine deaminase causes severe combined immunodeficiency with lymphopenia, defective proliferative responses to mitogens, hypogammaglobulinemia, and inability to mount specific antibody responses. Patients with low residual enzyme activity have later onset and slower loss of immune function. The enzymatic defect is expressed in all cells, making it a systemic metabolic disorder. The absence of the enzyme causes accumulation of lymph-toxic deoxyadenosine triphosphate, which inhibits ribonucleotide reductase, impairing lymphocyte development and function.
A retrospective single-centre study of seven patients diagnosed between 2012 and 2024 reported a median age at diagnosis of three months, with consanguinity in 86% of cases. Key symptoms included lymphopenia, recurrent infections, thymus absence, and systemic manifestations. Six patients received haematopoietic stem cell transplantation, two underwent matched donor transplantation, and one received gene therapy because no matched donor was available. Opportunistic infections included cytomegalovirus and recurrent skin infections. Two patients died of post-transplant complications.
The Canadian expert committee notes that patients with complete deficiency present in infancy with failure to thrive and recurrent bacterial, viral, and fungal infections, while those with partial deficiency may present later with milder symptoms and reduced T, B, and NK cell subpopulations. The committee provides management guidelines including a treatment algorithm for haematopoietic stem cell transplantation, gene therapy, and enzyme replacement therapy. What remains missing are prospective trials large enough to compare these treatment modalities directly, reliable biomarkers to predict which patients will benefit from which therapy, and funding for newborn screening programmes that could enable diagnosis before severe infections occur.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1975 · 250 citations
Severe Combined Immunodeficiency and Adenosine Deaminase Deficiency
AbstractBecause others had described a lack of the enzyme adenosine deaminase as associated with severe combined immunodeficiency, we surveyed kindreds with infants affected with such an immunodeficiency. Three infants in two families with severe combined immunodeficiency were found to have no detectable erythrocyte adenosine deaminase. Eleven family members heterozygous for adenosine deaminase deficiency were encountered among the first-degree relatives; adenosine deaminase deficiency and severe combined immunodeficiency were associated and inherited as autosomal recessive traits in both kindreds. Successful bone-marrow transplantation was carried out in two of these infants. Normal immunologic function was established in both children, but the deficiency of adenosine deaminase persisted in their erythrocytes. The enzyme deficiency did not impair the successful establishment of normal humoral and cellular immunity by transplants of bone-marrow cells from siblings who were either normal or heterozygous for adenosine deaminase deficiency.
New England Journal of Medicine · 1996 · 116 citations · open access
Hepatic Dysfunction as a Complication of Adenosine Deaminase Deficiency
AbstractComplete deficiency of adenosine deaminase causes severe combined immunodeficiency that is inherited as an autosomal recessive trait. The patients present in infancy with recurrent infections, lymphopenia, defective proliferative responses to mitogens, hypogammaglobulinemia, and an inability to mount specific antibody responses. Patients with a low level of residual adenosine deaminase activity have a later onset of clinical disease owing to a slower and sometimes less complete loss of immune function.1–3 Unlike other primary immunodeficiencies caused by defects in lymphocyte signaling pathways,4 adenosine deaminase deficiency is a systemic metabolic disorder. The enzymatic defect is expressed in all cells, and therefore the . . .
A case of severe combined immunodeficiency caused by adenosine deaminase deficiency with a new mutation
AbstractAdenosine deaminase (ADA) deficiency is among the most common causes of severe combined immunodeficiency, characterized by dysfunction of the T, B, and natural killer (NK) cells (T-B-NK-SCID) and severe lymphopenia.1 ADA is a key enzyme in the purine salvage pathway, the absence of which causes lymph-toxic deoxyadenosine triphospate (dATP) accumulation, inhibiting ribonucleotide reductase, a critical enzyme for DNA replication and repair. This effect impairs the lymphocyte development and function resulting in severe combined immune deficiency (SCID).
Çocuk Dergisi / Journal of Child · 2025 · 1 citations · open access
Evaluation of Patients with Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency: A Single-Center Experience
AbstractObjective: This study aimed to evaluate the clinical, immunological, and prognostic features of seven patients diagnosed with Adenosine Deaminase Deficiency Severe Combined Immunodeficiency (ADA-SCID) at Marmara University. The aim of this study was to enhance the recognition and management of this condition, which is characterized by impaired lymphocyte development and early severe infections. Methods: This retrospective study included seven patients with ADA-SCIDs who were monitored from 2012 to 2024. Patient data, including demographics, clinical findings, laboratory results, and imaging, were retrieved from hospital records. Diagnostic criteria focused on ADA enzyme activity and genetic mutations. Treatment regimens, such as immunoglobulin replacement, antimicrobial prophylaxis, enzyme replacement therapy, and hematopoietic stem cell transplantation (HSCT), were documented. Statistical analyses were performed using descriptive methods. Results: The cohort (6 males, 1 female) presented a median age at diagnosis of 3 months. Consanguinity was observed in 86% of cases. Key symptoms included lymphopenia, recurrent infections, thymus absence, and systemic manifestations. Six patients received HSCT, and two underwent matched donor transplantation. One patient received gene therapy because of the absence of a matched donor. Opportunistic infections were prevalent, including cytomegalovirus and recurrent skin infections noted. Overall, two patients died of post-HSCT complications. Conclusions: ADA-SCID is a life-threatening condition characterized by early severe infections and systemic manifestations. Early diagnosis and tailored treatment, including HSCT and gene therapy, are essential for improving survival outcomes. This study emphasizes the importance of early diagnosis to improve the survival and management outcomes of patients with ADA-SCID.
Report of the Canadian Expert Committee on the management of ADA deficiency
AbstractAdenosine deaminase (ADA) deficiency is a form of severe combined immunodeficiency. Aberrant mutations in the ADA gene result in loss of ADA activity and the toxic accumulation of metabolites that damage both immune and non-immune organs. While patients with complete ADA deficiency present during infancy with failure to thrive, recurrent bacterial, viral and fungal infections, those with incomplete (partial) deficiency may present at a later age with milder symptoms associated with reduced T, B, and NK cell subpopulations. Based on experience in Canadian centres, we provide management guidelines for patients with ADA deficiency, including a treatment algorithm for use of hematopoietic stem cell transplantation, gene therapy, and enzyme replacement therapy. Statement of novelty: Herein, we define guidelines for the management and treatment of patients with ADA deficiency.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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