DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency, common variable, 2 — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleImmunodeficiency, common variable, 2 maps to a 3-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 immunodeficiency, common variable, 2 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
complement C3d receptor 2 (CR2) — CR2 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 ndgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1GHQ · 2.04 Å · ligand 2-acetamido-2-deoxy-alpha-D-glucopyranose (NDG). Experimental structure, not a prediction.
What the evidence adds up to
The 2024 study of 185 patients suspected of immunodeficiency in Mashhad found that 12% received a genetic diagnosis of common variable immunodeficiency (CVID). Pneumonia was the most common clinical manifestation, occurring in 33.51% of the whole cohort. In 37.04% of all identified genes across the cohort, there was a discrepancy between the clinical and genetic diagnosis. The 2009 review notes that CVID disorders are a mixed, heterogeneous group linked by lack of immunoglobulin production and primary antibody failure, and that this variability makes it difficult to make coherent sense of immunopathogenesis or the role of various reported genetic abnormalities. The review states that collating complications and defining clinical phenotypes may improve accuracy of prognosis and management, but adds that these definitions need to be refined and confirmed by other studies.
The 2014 phase 1 study of sunitinib in HIV-positive patients with cancer, which stratified patients by whether their antiretroviral therapy included ritonavir, reported that no patient achieved a response. Ten of 19 patients had stable disease, including eight with prolonged disease stability. Patients on non-ritonavir HAART tolerated standard sunitinib dosing (50 mg/day) with no dose-limiting toxicity. In the ritonavir-based arm, a dose-limiting toxicity occurred at 37.5 mg, and three of five patients experienced grade 3 neutropenia, an uncommon toxicity of sunitinib. The 1992 review notes that patients with AIDS have a higher incidence of adverse reactions to drugs commonly used for opportunistic infections than non-AIDS patients, and that multiple drug prescriptions create a great potential for drug interactions.
What is still missing is a coherent genetic and immunopathological framework that can reliably stratify CVID patients for targeted interventions. The 2024 study’s finding of a 37% discrepancy between clinical and genetic diagnosis underscores that current genetic panels are not definitive. No trial has tested sunitinib or any other repurposed kinase inhibitor specifically in CVID patients. The necessary funding for such a trial, a trial design that accounts for the heterogeneity of CVID, and a method to identify which patients might benefit from any given drug remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Haematology · 2009 · 392 citations · open access
Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions
AbstractThe common variable immunodeficiency disorders are a mixed group of heterogeneous conditions linked by lack of immunoglobulin production and primary antibody failure. This variability results in difficulty in making coherent sense of either immunopathogenesis or the role of various genetic abnormalities reported in the literature. The recent attempt to collate the varied complications in these conditions and to define particular clinical phenotypes has improved our understanding of these diseases. Once refined and confirmed by other studies, these definitions will facilitate improved accuracy of prognosis and better management of clinical complication. They may also provide a method of analysing outcomes as related to new immunopathological and genetic findings.
A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus‐positive patients with cancer: AIDS Malignancy Consortium trial AMC 061
AbstractBACKGROUND: The treatment of non-acquired immunodeficiency syndrome-defining cancers may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium to assess targeted therapies and HAART in human immunodeficiency virus-positive patients (ClinicalTrials.gov identifier: NCT00890747). METHODS: In a modified phase 1 study of sunitinib, patients were stratified into 2 treatment arms based on whether they were receiving therapy with ritonavir, a potent CYP3A4 inhibitor. Patients in treatment arm 1 (non-ritonavir HAART) received standard sunitinib dosing (50 mg/day). Treatment arm 2 (ritonavir-based HAART) used a phase 1, 3 + 3 dose escalation design (from 25 mg/day to 50 mg/day). Cycles were comprised of 4 weeks on treatment followed by a 2-week break (6 weeks total). The pharmacokinetics of sunitinib and its active metabolite (N-desethyl sunitinib) were assessed. RESULTS: Nineteen patients were enrolled and were evaluable. Patients on treatment arm 1 tolerated treatment with no dose-limiting toxicity observed. In treatment arm 2, a dose-limiting toxicity was experienced at a dose of 37.5 mg, and an additional 3 of 5 patients experienced grade 3 neutropenia (toxicity graded as per National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]), an uncommon toxicity of sunitinib. No patient achieved a response, but 10 patients had stable disease, including 8 with prolonged disease stability. Efavirenz, a potent inducer of CYP3A4, resulted in increased exposure of N-desethyl sunitinib, whereas ritonavir caused decreased exposure of the metabolite. Hand-foot syndrome was associated with higher steady-state trough concentrations of sunitinib. CONCLUSIONS: Patients receiving non-ritonavir-based HAART regimens tolerated standard dosing of sunitinib. Patients receiving ritonavir-based therapy who were treated with a dose of 37.5 mg/day experienced higher toxicities. Dose reductions of sunitinib to 37.5 mg may be warranted in patients receiving ritonavir.
Current Opinion in Infectious Diseases · 1992 · 15 citations
Drug interactions and toxicities in patients with AIDS
AbstractThe potential for drug interactions leading to adverse reactions is great in patients with the acquired immunodeficiency syndrome, since multiple drugs are commonly prescribed to these patients. In addition, patients with acquired immunodeficiency syndrome have a higher incidence of adverse reactions to drugs that are commonly used in the treatment of opportunistic infections than non-acquired immunodeficiency syndrome patients. As a result of the high rate of adverse reactions, drugs that are currently available are often limited in their use. An appreciation of the potential drug interactions and knowledge of the most frequently occurring adverse reactions can increase the chance of a successful therapeutic response.
Immunology and Genetics Journal · 2024 · 0 citations
Genetic Evaluation of Patients Suspected of Immunodeficiency Referred to the Immunodeficiency Clinic of Akbar Hospital in Mashhad
AbstractBackground: The purpose of this study was genetic evaluation of patients suspected of immunodeficiency, without a definitive diagnosis, referred to the Immunodeficiency Clinic of Akbar Hospital in Mashhad in 2021-2022. Methods: In this study, patients suspected of immunodeficiency, without a definitive diagnosis, referred to an immunodeficiency clinic were included A complete clinical and paraclinical examination has been done by expert specialists and clinical geneticists. Blood samples were taken for genetic analysis using the Exome Sequencing technique followed by comprehensive bioinformatics analysis. Parents and healthy offspring were assessed for the candidate gene variants. Results: In this study, 185 patients were included; 58.56% of them were male; The average age of the participants was 9.28±5.40 years, and consanguineous marriage of parents was observed in 79.8 % of cases. Pneumonia with 33.51% was the most common clinical manifestation in patients with suspected immunodeficiency. In total, 41.14% of patients suffered from combined immunodeficiency, 26 .86% of them had defects of phagocyte number, function, or both; and 24% had predominantly antibody deficiencies. Hyper IgE syndrome was detected in 16% of patients, SCID and CGD each in 14.86% of patients, CVID in 12% of patients, and LAD in 7.43% of them. In 37.04% of the identified genes, there was a discrepancy between clinical and genetic diagnosis in patients. Conclusion: The most common clinical manifestation of patients suspected of primary immunodeficiency is pneumonia; therefore, patients who suffer from recurrent respiratory infections should be checked for genetic immunodeficiency. In this study, most patients were in the groups of immunodeficiencies affecting multiple cell types, defects of phagocyte number, function, or both; and predominantly antibody deficiencies, respectively. The most common diseases diagnosed were: Hyper IgE syndrome, SCID and CGD, CVID, and LAD.
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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