DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyper-IgM syndrome — 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 moduleHyper-IgM syndrome 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 hyper-igm 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
CD40 ligand (CD40LG) — CD40LG 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 tmodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6W9G · 1.82 Å · ligand trimethylamine oxide (TMO). Experimental structure, not a prediction.
What the evidence adds up to
The 2002 review describes hyper-IgM syndrome as a primary immunodeficiency characterised by defects in the CD40/CD40L signalling pathway. It states that molecular diagnosis may help provide the most appropriate treatment and prognosis, but offers no clinical trial data or treatment outcomes.
A 2009 report describes two patients with intrinsic B-cell class-switch defects, a subclass of hyper-IgM syndromes, who had long-standing lymphoproliferation and autoimmunity. After a definite individual diagnosis was established, both patients started rituximab therapy. Autoimmune phenomena and generalised lymphadenopathy disappeared and remained well controlled during an observation period of 3–4 years, without adverse effects. Quality of life increased remarkably in both patients. This is a report of two patients, not a controlled trial.
A 2024 case report describes hyper-IgM syndrome revealed by persistent chronic neutropenia in an infant. It notes that clinical manifestations are dominated by recurrent respiratory and digestive infections. No treatment or outcome data are provided.
A 1937 letter on hypersensitivity to acetylsalicylic acid (aspirin) has no relevance to hyper-IgM syndrome.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Allergy and Clinical Immunology · 2002 · 38 citations
Cross-talk between CD40 and CD40L: lessons from primary immune deficiencies
AbstractPURPOSE OF REVIEW: The purpose of this review is to provide an update of the molecular bases of CD40-mediated signalling and of the human immune defects associated with abnormalities of this activation pathway. RECENT FINDINGS: Over the last years considerable progress in the identification of intracellular molecules mediating CD40 signalling has been achieved. This review focuses on the recent work on the molecular mechanisms of CD40 signalling mediated by tumor necrosis factor receptor-associated factors, by transcription of the activation-induced cytidine deaminase gene and by activation of nuclear factor kappa B. Furthermore, the importance of CD40/CD40L interaction for the induction of adaptive immunity will be outlined in the context of primary immunodeficiencies due to defects of the genes involved in the CD40 signalling pathway, which are characterized by an immunological phenotype of hyper-IgM syndrome. SUMMARY: The critical role of CD40/CD40L interactions in the development of various disease states has been fully appreciated, and further understanding of the molecular events involved in CD40 signalling may allow the identifications of candidate genes for other hyper-IgM syndromes. Molecular diagnosis will help to provide the most appropriate treatment and prognosis.
British Journal of Haematology · 2009 · 12 citations
Successful treatment of autoimmune and lymphoproliferative complications of patients with intrinsic B‐cell immunodeficiencies with Rituximab
AbstractThe heterogeneous group of primary immunodeficiencies requires personalized diagnosis and therapy to acheive an optimal outcome for each patient. This was exemplified by two patients with intrinsic B-cell class-switch defects (subclass of Hyper-IgM syndromes), where lymphoproliferation and autoimmunity determined the clinical course for many years due to lack of exact diagnosis. Based on genetics or a novel functional diagnostic approach, a definite individual diagnosis was established for each patient and they started Rituximab therapy. Autoimmune phenomena and generalized lymphadenopathy disappeared and remained well controlled during the observation period (3-4 years) without adverse effects. Quality of life increased remarkably in both patients.
International Journal of Advanced Research · 2024 · 0 citations · open access
CHRONIC NEUTROPENIA REVEALING HYPER IGM SYNDROME: A CASE REPORT
AbstractHyper IgM syndrome is a well-knownhereditaryimmunodeficiency, first describedin 1961. It iscaused by a defect in B lymphocytes, characterized by a normal or high serumlevel of IgM and a low or zerolevel of IgG, IgA, IgE resultingfrom a deficiency in isotype switching. Itsclinical manifestations are dominated by recurrent infections, especiallyrespiratory and digestive. The interest of this article is to illustrate a particular mode of revelation of hyper IgM syndromes through persistent chronicneutropenia in an infant.
Abstract<h3>To the Editor:—</h3> In our paper "Hypersensitivity to Acetylsalicylic Acid (Aspirin)," Dr. Buchstein and I point out the serious reactions that occasionally occur following the ingestion of acetylsalicylic acid. We are aware that this remedy has been used by many allergic individuals without ill effects; one of our patients in fact estimated that he took 4,000 tablets (5 grains each) of acetylsalicylic acid a year for his asthma without encountering any trouble. However, it seemed to us very significant that sixty-one of the sixty-two individuals found sensitive to this drug had other allergic manifestations themselves or were from definitely allergic families. Nine additional patients hypersensitive to acetylsalicylic acid have been encountered since completing the study, and these also had other evidence of major allergy without exception. Since we found the reactions to acetylsalicylic acid very severe, at times even grave, and since we believe the incidence of sensitivity to acetylsalicylic
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.
