DeCure for Immunodeficiency-centromeric instability-facial anomalies syndrome
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for immunodeficiency-centromeric instability-facial anomalies 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 moduleImmunodeficiency-centromeric instability-facial anomalies 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 immunodeficiency-centromeric instability-facial anomalies 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
DNA methyltransferase 3 beta (DNMT3B) — DNMT3B 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 sahdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6PA7 · 2.94 Å · ligand S-ADENOSYL-L-HOMOCYSTEINE (SAH). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 44 ICF patients, 23 had mutations in DNMT3B (ICF1), 13 had mutations in ZBTB24 (ICF2), and for 8 patients the gene defect was not identified (ICFX). The humoral immunodeficiency is generally more pronounced in ICF1 patients, but B- and T-cell compartments are involved in both ICF1 and ICF2. ICF2 patients have a significantly higher incidence of intellectual disability. Congenital malformations can be observed in some ICF1 and ICF2 cases. Patients without immunodeficiency but with only facial dysmorphism and intellectual deficit exist.
A 14-month-old female child with ICF1, born of third-degree consanguinity, had recurrent admissions for fever, cough, and cold seven times, with two intensive care unit stays for pneumonia, a urinary tract infection at 4 months, febrile seizures at 9 months, and left otitis media at 13 months. There was a family history of early neonatal deaths in two male siblings and one maternal male cousin. Immunological investigations showed hypogammaglobulinemia with diminished levels of IgG and IgA. Allogeneic haematopoietic cell transplantation in patients with severe disease corrects the immunodeficiency and improves growth.
No drug treatment is described in any of these abstracts. The only intervention reported to correct the immunodeficiency is allogeneic haematopoietic cell transplantation, which is not a drug. What is missing is any controlled trial of a pharmacological agent, any evidence that a drug can reverse the epigenetic defect or the intellectual disability, and any stratification of patients by genotype to test targeted therapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuropediatrics · 2014 · 0 citations
Immunodeficiency, Centromeric Instability, Facial Anomalies Syndrome Type 2 (ICF2): Combined Immunodeficiency, Autoimmune Phenomena, and Intellectual Disability
AbstractIntroduction: The immunodeficiency, centromeric instability, facial anomalies syndrome (ICF) is a rare autosomal recessive disease defined by immunodeficiency, developmental delay, and facial abnormalities. Centromeric instability results in chromosomal rearrangements and genomic methylation is due to a defect. ICF1 and 2 are caused by biallelic mutations in the DNA methyltransferase 3B gene DNMT3B and the zinc finger and BTB domain-containing 24 gene ZBTB24, respectively. Patients without immunodeficiency but only with facial dysmorphism and intellectual deficit exist.
Zurich Open Repository and Archive (University of Zurich) · 2013 · 0 citations · open access
Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects
AbstractImmunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF syndrome: DNMT3B and ZBTB24. To characterize the clinical features of this syndrome, as well as genotype-phenotype correlations, we compared clinical and genetic data of 44 ICF patients. Of them, 23 had mutations in DNMT3B (ICF1), 13 patients had mutations in ZBTB24 (ICF2), whereas for 8 patients, the gene defect has not yet been identified (ICFX). While at first sight these patients share the same immunological, morphological and epigenetic hallmarks of the disease, systematic evaluation of all reported informative cases shows that: (1) the humoral immunodeficiency is generally more pronounced in ICF1 patients, (2) B- and T-cell compartments are both involved in ICF1 and ICF2, (3) ICF2 patients have a significantly higher incidence of intellectual disability and (4) congenital malformations can be observed in some ICF1 and ICF2 cases. It is expected that these observations on prevalence and clinical presentation will facilitate mutation-screening strategies and help in diagnostic counseling.
Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects
AbstractImmunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a primary immunodeficiency, predominantly characterized by agammaglobulinemia or hypoimmunoglobulinemia, centromere instability and facial anomalies. Mutations in two genes have been discovered to cause ICF syndrome: DNMT3B and ZBTB24. To characterize the clinical features of this syndrome, as well as genotype–phenotype correlations, we compared clinical and genetic data of 44 ICF patients. Of them, 23 had mutations in DNMT3B (ICF1), 13 patients had mutations in ZBTB24 (ICF2), whereas for 8 patients, the gene defect has not yet been identified (ICFX). While at first sight these patients share the same immunological, morphological and epigenetic hallmarks of the disease, systematic evaluation of all reported informative cases shows that: (1) the humoral immunodeficiency is generally more pronounced in ICF1 patients, (2) B- and T-cell compartments are both involved in ICF1 and ICF2, (3) ICF2 patients have a significantly higher incidence of intellectual disability and (4) congenital malformations can be observed in some ICF1 and ICF2 cases. It is expected that these observations on prevalence and clinical presentation will facilitate mutation-screening strategies and help in diagnostic counseling.
Immunodeficiency, Centromeric Region Instability, Facial Anomalies Syndrome 1
AbstractAllogeneic hematopoietic cell transplantation (HCT) in patients with severe disease corrects the immunodeficiency and improves growth. Case DesCriptionA 14-month-old female child born of third-degree consanguinity, full term with history of recurrent admissions for fever, cough, cold-7 times, and intensive care unit (ICU) stay twice at 4 and 9 months of age for pneumonia, urinary tract infection at 4 months of age, febrile seizures at 9 months of age, and left otitis media at 13 months of age.There was a family history of early neonatal deaths in two male siblings and one maternal male cousin.At 13 months of age, a detailed assessment was conducted due to recurring infections.The results of immunological investigations demonstrated the presence of hypogammaglobulinemia, which is characterized by diminished levels of IgG and IgA in the serum.
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.
