DeCure for Combined immunodeficiency due to OX40 deficiency
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for combined immunodeficiency due to OX40 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 OX40 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 ox40 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
TNF receptor superfamily member 4 (TNFRSF4) — TNFRSF4 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2HEY · 2.0 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not describe any clinical trial or treatment for combined immunodeficiency due to OX40 deficiency. The 2014 review discusses immunoglobulin therapy for antibody deficiencies in general, not specifically for OX40 deficiency. The 2001 study examines OX40 stimulation in HIV-1 infection using cell lines, showing that OX40-gp34 interaction enhances HIV-1 production in vitro, and that this effect can be blocked by a monoclonal antibody. The 2013 chapter covers CD40 and CD40 ligand deficiencies, a separate condition. No data on survival, response rates, or sample sizes for any treatment in OX40 deficiency are reported in these abstracts.
There is no evidence in these abstracts that immunoglobulin therapy has been tested or shown to be effective in patients with OX40 deficiency. The 2001 paper is an in vitro study on HIV-1, not a clinical study of OX40 deficiency. The 2013 chapter describes a different immunodeficiency. The abstracts contain no information on any drug being used to treat OX40 deficiency in humans.
What is missing is any clinical trial, case series, or even a single patient report testing any treatment for combined immunodeficiency due to OX40 deficiency. No funding for such a trial is mentioned, no trial design exists in the literature provided, and no patient stratification has been attempted. The basic natural history of the condition and its response to any intervention remain unstudied in these sources.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Immunotherapy · 2014 · 62 citations · open access
An Update on the Use of Immunoglobulin for the Treatment of Immunodeficiency Disorders
AbstractFor patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement.
Journal of Virology · 2001 · 35 citations · open access
OX40 Stimulation by gp34/OX40 Ligand Enhances Productive Human Immunodeficiency Virus Type 1 Infection
AbstractOX40 is a member of the tumor necrosis factor (TNF) receptor superfamily and known to be an important costimulatory molecule expressed on activated T cells. To investigate the role of costimulation of OX40 in human immunodeficiency virus type 1 (HIV-1) infection by its natural ligand, gp34, the OX40-transfected ACH-2 cell line, ACH-2/OX40, chronically infected with HIV-1, was cocultured with paraformaldehyde (PFA)-fixed gp34-transfected mouse cell line, SV-T2/gp34. The results showed that HIV-1 production was strongly induced. This was followed by apparent apoptosis, and both processes were specifically inhibited by the gp34-specific neutralizing monoclonal antibody 5A8. Endogenous TNF alpha (TNF-alpha) and TNF-beta production were not involved in the enhanced HIV-1 production. Furthermore, enhanced HIV-1 transcription in gp34-stimulated ACH-2/OX40 cells was dependent on the kappa B site of the HIV-1 long terminal repeat, and the OX40-gp34 interaction activated NF-kappa B consisting of p50 and p65 subunits. When primary activated CD4(+) T cells acutely infected with HIV-1(NL4-3) (CXCR4-using T-cell-line-tropic) were cocultured with PFA-fixed gp34(+) human T-cell leukemia virus type 1-bearing MT-2 cells or SV-T2/gp34 cells, HIV-1 production was also markedly enhanced. The enhancement was again significantly inhibited by 5A8. The present study first shows that OX40-gp34 interaction stimulates HIV-1 expression and suggests that OX40 triggering by gp34 may play an important role in enhancing HIV-1 production in both acutely and latently infected CD4(+) T cells in vivo.
LymphoSign Journal · 2017 · 8 citations · open access
CD40 DEFICIENCY: A UNIQUE ADULT PATIENT WITH HYPER IMMUNOGLOBULIN M SYNDROME AND NORMAL EXPRESSION OF CD40
AbstractBackground: CD40 deficiency is an autosomal recessive, combined primary immunodeficiency characterized by defects of immunoglobulin class switch recombination and somatic hypermutation. It is part of an expanding group of diseases collectively known as hyper immunoglobulin M syndromes. Clinical manifestations of the disease usually begin early in life with recurrent sinopulmonary bacterial infections and susceptibility to opportunistic organisms. Only 16 patients from 12 unrelated families have been reported to date, all with lack of membrane expression of CD40 molecule.
Oxford University Press eBooks · 2013 · 0 citations
CD40 and CD40 Ligand Deficiencies
AbstractPrimary immunodeficiency diseases are inherited disorders that affect human adaptive and innate immunity. In most cases, affected individuals experience recurrent infections, but they may also suffer from autoimmune diseases and malignancies. This chapter focuses on CD40 and CD40 Ligand Deficiencies,including the historic and scientific background, clinical presentations, immunologic characteristics, and the molecular/genetic underpinnings. Where appropriate, diagnostic tools and therapeutic options are outlined -- from prophylactic anti-infective measures to hematopoietic stem cell transplantation and gene therapy.
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.
