DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for X-linked hyper-IgM syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleX-linked hyper-IgM syndrome maps to a 2-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 x-linked 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
X-linked hyper-IgM syndrome is a rare primary immunodeficiency caused by mutations in the CD40LG gene, which encodes the CD40 ligand. In a 2007 report, a 19-year-old male patient with the syndrome developed progressive multifocal leukoencephalopathy. His serum IgA was decreased, IgM slightly increased, and IgG normal due to monthly immunoglobulin infusions. CD40 ligand expression on T cells was markedly reduced. Magnetic resonance imaging showed confluent lesions involving most of the right hemisphere with a mass effect. The patient died after six weeks despite combined antiviral treatment. The authors concluded that progressive multifocal leukoencephalopathy may follow a rapid course in these patients because of global defects in cellular and B cell responses.
A 2021 study identified three patients with X-linked hyper-IgM syndrome in Ho Chi Minh City, Vietnam. All had symptoms including recurrent sinopulmonary infections, oral ulcers, and otitis media, but diagnosis was significantly delayed. Two patients had elevated IgM levels, and all three had low IgG levels. One patient developed anti-phospholipid syndrome, which the authors state is documented for the first time in this syndrome. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation (c.156+2T>A) and two previously characterised mutations (c.436_438delTAC and c.654C>A). Western blot analysis showed that CD40 ligand was not expressed in any of the three patients.
A 1996 database, CD40Lbase, catalogued mutations in the CD40L gene causing X-linked hyper-IgM syndrome, compiling information from that database and other literature. No treatment outcomes or survival data are reported in that entry.
What is still missing is systematic data on long-term outcomes for patients diagnosed early, prospective trials of any targeted therapy, and understanding of why some patients develop rare complications such as anti-phospholipid syndrome or progressive multifocal leukoencephalopathy while others do not. Patient stratification by specific CD40LG mutation type remains largely unexplored in relation to prognosis.
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 Neurology · 2007 · 19 citations
X-linked Hyper-IgM Syndrome Associated With a Rapid Course of Multifocal Leukoencephalopathy
AbstractOBJECTIVE: To report an exceptional association between X-linked hyper-IgM syndrome and progressive multifocal leukoencephalopathy. DESIGN: Clinical, immunological, and histological analysis. Patient A 19-year-old male patient with X-linked hyper-IgM syndrome developed typical signs and symptoms of progressive multifocal leukoencephalopathy. RESULTS: The serum level of IgA was decreased; the serum level of IgM was slightly increased; and the serum level of IgG was normal as a result of monthly infusions of immunoglobulin. The expression of CD40 ligand on T cells was markedly reduced in the patient. Magnetic resonance imaging indicated confluent lesions involving the majority of the right hemisphere with a mass effect. The patient died after 6 weeks despite combined antiviral treatment. CONCLUSION: Progressive multifocal leukoencephalopathy may follow a rapid course in patients with X-linked hyper-IgM syndrome because of global defects of cellular and B cell responses.
Molecular Genetics & Genomic Medicine · 2021 · 8 citations · open access
<i>CD40LG</i> mutations in Vietnamese patients with X‐linked hyper‐IgM syndrome; catastrophic anti‐phospholipid syndrome as a new complication
AbstractBACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a rare primary immunodeficiency caused by CD40 ligand defects. METHODS: We identified three patients with XHIGM in Ho Chi Minh City, Vietnam. Whole-exome sequencing, immunological analyses and western blot were performed to investigate phenotypic and genotypic features. RESULTS: Despite showing symptoms typical of XHIGM, including recurrent sinopulmonary infections, oral ulcers and otitis media, the diagnosis was significantly delayed. One patient developed anti-phospholipid syndrome, which has been documented for the first time in XHIGM syndrome. Two patients had elevated IgM levels and all of them had low IgG levels. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation c.156+2T>A and two previously characterised mutations (non-frameshift deletion c.436_438delTAC, stop-gain c.654C>A). Due to these mutations, the CD40 ligand was not expressed in any of the three patients, as demonstrated by western blot analysis. CONCLUSION: This is the first report of XHIGM syndrome in Vietnam indicates that an effective diagnostic strategy, such as sequencing analysis, contributes to reliable diagnosis and subsequent therapy.
IRIS Research product catalog (Sapienza University of Rome) · 1996 · 0 citations
CD40lbase: a database of CD40L gene mutations causing X-linkedhyper-IgM syndrome
AbstractX-linked hyper-IgM syndrome (X-HIM) is an immunodeficiency caused by mutations in the gene encoding the CD40 ligand (CD40L). A database (CD40Lbase) of CD40L mutations has now been established, and the resultant information, together with other mutations reported elsewhere in the literature, is presented here.
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.
