DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for neutrophil immunodeficiency syndrome — 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 moduleNeutrophil immunodeficiency syndrome 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 neutrophil immunodeficiency syndrome 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
Rac family small GTPase 2 (RAC2) — RAC2 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1DS6 · 2.35 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In 1992, granulocyte-macrophage colony-stimulating factor (GMCSF) was studied in HIV infection because both the virus and zidovudine (formerly AZT) can cause neutropenia. In vitro, GMCSF alone may stimulate HIV replication, but in the presence of zidovudine a synergistic inhibition of replication occurs. Early clinical studies in AIDS patients showed that GMCSF can raise neutrophil counts with or without concurrent zidovudine. The abstract states that long-term safety and tolerance of the combination had yet to be established.
A 2022 study compared neutrophil counts in visceral leishmaniasis (VL) patients, VL/HIV co-infected patients, and controls. At time of diagnosis, median neutrophil counts were measured in controls (n=25), VL patients (n=41), and VL/HIV patients (n=37). At end of treatment, at 3 months, and at 6–12 months post-treatment, the VL/HIV group consistently showed lower neutrophil counts than the VL-only group, though the abstract does not report the exact median values or p-values for each comparison. Among VL/HIV patients, those who relapsed after successful anti-leishmanial treatment (n=23) had neutrophil counts that were not statistically different from those who did not relapse (n=39) during the 3-month and 6–12-month follow-up periods (ns = not significant).
A 2020 study found that HIV-1 infection is associated with a higher frequency of immature low-density neutrophils (imLDNs, defined as CD16−CD64+). These imLDNs have a reduced capacity for reactive oxygen species production and phagocytosis. Total neutrophil phenotype was altered in HIV-1/AIDS, with decreased CD16 and increased CXCR4 and CD10 expression, and there were changes in neutrophil metabolism including increased expression of genes related to oxidative phosphorylation and mTOR signaling. The observed changes in neutrophil populations correlated with CD4+ T cell count, level of liver fibrosis, and arterial stiffness, suggesting a role for these cells in HIV-1/AIDS pathogenesis.
What is still missing is a randomised trial testing GMCSF plus zidovudine specifically in patients with neutrophil immunodeficiency syndrome, with long-term safety data and clear endpoints for infection reduction. The 2022 VL/HIV data show no significant difference in neutrophil counts between relapsers and non-relapsers, so the prognostic value of neutrophil counts in that setting remains uncertain. Patient stratification by neutrophil subset phenotype, as described in the 2020 study, has not been incorporated into a treatment trial. Funding for such a trial, and for the development of a standardised assay for immature neutrophils, is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Internal Medicine · 1993 · 196 citations
New Insights into Common Variable Immunodeficiency
AbstractCommon variable immunodeficiency (CVI) is a heterogenous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome also have an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by various medical specialists. This review discusses the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI.
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.
Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · 1992 · 4 citations
Granulocyte‐Macrophage Colony‐Stimulating Factor and Zidovudine in the Treatment of Neutropenia and Human Immunodeficiency Virus Infection
AbstractGranulocyte-macrophage colony-stimulating factor (GMCSF) is a hematopoietic protein that has been studied both in vitro and in vivo in human immunodeficiency virus (HIV) infection. Since both HIV infection primarily and zidovudine (formerly AZT) treatment secondarily may result in neutropenia, administration of GMCSF to persons with HIV infection is generating considerable interest. Despite in vitro studies demonstrating that the agent may stimulate HIV replication, in the presence of zidovudine a synergistic inhibition of replication occurs. Early clinical studies in patients with the acquired immunodeficiency syndrome indicate that GMCSF can raise neutrophil counts with or without concurrent zidovudine treatment. The long-term safety and tolerance of the combination has to be established.
Comparison of neutrophil counts between VL and VL/HIV patients and controls over time.
Abstract<p>Neutrophil counts were measured in the whole blood of controls (n = 25), VL (ToD: n = 41, EoT: n = 42; 3m: n = 34, 6-12m: n = 22) and VL/HIV (ToD: n = 37, EoT: n = 36, 3m: n = 37, 6-12m: n = 20) patients as described in Material and Methods. <b>A.</b> Comparison of neutrophil counts over time in VL, VL/HIV and controls. <b>B.</b> Comparison of neutrophil counts from VL/HIV patients who did not relapse (n = 39) and those who relapsed (n = 23) after successful anti-leishmanial treatment, during the 3m and 6–12 follow-up period. If a patient did not relapse during the two-time points of follow-up and if a patient relapsed at both 3 and 6–12 months, this is represented as 2 measurements. Each symbol represents the value for one individual. Results are presented as median with interquartile range. Statistical differences between VL and VL/HIV patients at each time point or between VL/HIV patients who did not relapse and those who relapsed were determined using a Mann-Whitney test and statistical differences between the 4 different time points for each cohort of patients were determined by Kruskal-Wallis test. ToD = Time of Diagnosis; EoT = End of Treatment; 3m = 3 months post EoT; 6-12m = 6–12 months post EoT. ns = not significant.</p>
HIV-1 infection is associated with increased prevalence of immature neutrophils and alterations in total neutrophil phenotype and metabolic profile
AbstractAbstract Despite successful viral control, HIV-1-infected individuals have a higher risk of developing life-threatening comorbidities including liver and cardiovascular diseases which are associated with inflammation and immune dysregulation. However, the specific mediators driving these pathologies are not yet understood. Neutrophils are increasingly recognized as a heterogeneous population with critical roles in immune regulation and disease pathogenesis. Methods of neutrophil characterization developed in our laboratory have facilitated the identification of novel neutrophil subpopulations including two subsets of low-density neutrophils (LDNs). LDNs are known to be expanded in inflammatory conditions including cancers and chronic infections. The LDN subpopulations identified in our laboratory represent different maturation states as indicated by their distinct nuclear morphologies and phenotypic differences [mature (mLDNs) CD16+CD64Low and immature (imLNDs) CD16−CD64+]. Our findings indicate that imLDNs have a reduced capacity for reactive oxygen species production and phagocytosis. We present data demonstrating that HIV-1/AIDS is associated with a higher frequency of imLDNs and significant alterations in total neutrophil phenotype (decreased CD16 and increased CXCR4 and CD10), function, and metabolism including increased expression of genes related to oxidative phosphorylation and mTOR signaling. Observed changes in neutrophil populations correlate with key clinical parameters including CD4+ T cell count, level of liver fibrosis, and arterial stiffness suggesting an important role for these cells and specific subsets in the pathogenesis of HIV-1/AIDS and potentially other inflammatory diseases.
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.
