DeCure for Combined immunodeficiency due to CTPS1 deficiency
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for combined immunodeficiency due to CTPS1 deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCombined immunodeficiency due to CTPS1 deficiency maps to a 1-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 combined immunodeficiency due to ctps1 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
CTP synthase 1 (CTPS1) — CTPS1 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 utpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7MGZ · 2.8 Å · ligand URIDINE 5'-TRIPHOSPHATE (UTP). Experimental structure, not a prediction.
What the evidence adds up to
A 2022 case report describes the first presentation of CTPS1 deficiency with coccidioidomycosis, a fungal infection. The abstract states that CTPS1 deficiency is a combined immunodeficiency that impairs lymphocyte proliferation, but provides no survival data, response rates, or sample sizes beyond the single patient. No other abstract in this set concerns CTPS1 deficiency or its treatment.
The remaining abstracts cover unrelated conditions. A 1992 study of 222 episodes of Pneumocystis carinii pneumonia in AIDS patients found survival rates of 86% for first episodes, 84% for second, and 88% for third, with no significant difference between them. A 1998 screening of 44 patients with common variable immunodeficiency found no cases of adenosine deaminase or purine nucleoside phosphorylase deficiency. A 2017 paper describes two patients with other primary immunodeficiencies (CTLA-4 haploinsufficiency and APDS/PASLI) but not CTPS1 deficiency. A 2025 report on PNKP deficiency describes two siblings with hypogammaglobulinemia and reduced class-switched memory B cells, but again does not involve CTPS1.
No drug is mentioned in any abstract for CTPS1 deficiency. There are no data on any treatment, no response rates, and no survival outcomes for this condition. What is missing is any clinical trial, any tested therapy, any patient cohort larger than one, and any stratification by genetic or clinical subtype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Internal Medicine · 1992 · 36 citations
Equal survival rates for first, second, and third episodes of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome
AbstractBACKGROUND: Second and subsequent episodes of acute Pneumocystis carinii pneumonia (PCP) are reported to have a worse prognosis than initial episodes in patients with the acquired immunodeficiency syndrome. We tested the hypothesis that survival rates of first, second, and subsequent episodes of acute PCP in patients with the acquired immunodeficiency syndrome are equal. METHODS: Analysis of the outcomes in prospective series of patients with the acquired immunodeficiency syndrome treated for acute PCP over 5 years. RESULTS: Survival rates of 222 PCP occurrences by episode number were: first, 86%; second, 84%; third, 88%; and fourth, 67%. Survival rates for the first, second, and third episodes were not significantly different. Second and third episodes had a larger proportion of patients with mild disease than initial episodes. CONCLUSIONS: Survival rates for first, second, and third episodes of PCP in patients with the acquired immunodeficiency syndrome are not different. In contrast to earlier articles, treatment for second and third episodes of acute PCP may be as successful as in initial episodes.
Clinical and Diagnostic Laboratory Immunology · 1998 · 29 citations · open access
Adenosine Deaminase Deficiency and Purine Nucleoside Phosphorylase Deficiency in Common Variable Immunodeficiency
AbstractThe clinical presentations of adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency are widely variable and include clinical and immunologic findings compatible with common variable immunodeficiency. The screening of 44 patients with common variable immunodeficiency failed to identify any individuals with deficiencies of these enzymes.
Journal of Pediatric Hematology/Oncology · 2017 · 11 citations
Clinical Challenges: Identification of Patients With Novel Primary Immunodeficiency Syndromes
AbstractNovel primary immunodeficiency disorders are being identified with next generation sequencing technologies. We describe 1 patient with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency who had recurrent enhancing brain lesions, nodular pulmonary infiltrates, hepatosplenomegaly, immune cytopenias, as well as progressive hypogammaglobulinemia and lymphopenia. We describe a second patient with activated p110δ syndrome (APDS)/p110δ activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI) in association with recurrent respiratory tract infections, Epstein-Barr virus infection, lymphadenopathy, elevated serum IgM, and progressive lymphopenia. These presentations highlight the need for astute clinical judgment in the evaluation of patients with potential primary immunodeficiency disorders.
Open Forum Infectious Diseases · 2022 · 4 citations · open access
Seronegative Mediastinal Coccidioidomycosis as a Novel Presentation of CTPS1 Combined Immunodeficiency
AbstractInborn errors of immunity may present with susceptibility to coccidioidomycosis. This is especially so in disorders impairing the interferon-γ and interleukin 12 signaling axis. We describe the first case of cytidine nucleotide triphosphate synthetase 1 (CTPS1) deficiency, a combined immunodeficiency impairing lymphocyte proliferation, presenting with coccidioidomycosis.
Journal of Allergy and Clinical Immunology Global · 2025 · 0 citations · open access
B-cell immunodeficiency associated with polynucleotide kinase 3′-phosphatase (PNKP) deficiency
AbstractBackground: DNA repair is crucial for maintaining genomic integrity and plays a significant role in the immune system. Defects in DNA repair pathways are often associated with immunodeficiency, including B-cell defects, which are consistent with the need for DNA repair during V(D)J recombination, class switching, and somatic hypermutation during B-cell maturation. Polynucleotide kinase 3'-phosphatase (PNKP) plays a significant role in DNA repair. PNKP deficiency is characterized by neurologic developmental abnormalities; however, immunodeficiency has not yet been reported. Objective: We focused on a pair of PNKP-deficient siblings who presented with microcephaly, eye abnormalities, and hypogammaglobulinemia. We aimed to analyze the effect of PNKP deficiency on B-cell development. Methods: Whole-exome sequencing was performed to identify the genetic cause of hypogammaglobulinemia. DNA repair efficiency was analyzed using patient-derived fibroblasts. The immune phenotype and B-cell receptor repertoire were analyzed using the patient's peripheral blood, alongside other patients with PNKP deficiency without severe immunodeficiency. Results: variants. Fibroblasts revealed defects in DNA repair in response to radiation-induced double/single-stranded DNA breaks. Flow cytometry revealed reduced total B-cell and class-switched memory B-cell counts. The B-cell receptor repertoire analysis demonstrated reduced frequencies of somatic hypermutations in these patients, whereas other patients with PNKP deficiency exhibited normal B-cell receptor repertoire patterns. Conclusion: variant-induced DNA repair abnormalities may be associated with immunodeficiency.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
