DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Omenn syndrome — screening already-approved drugs against its 15-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleOmenn syndrome maps to a 15-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 omenn 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
adenosine deaminase (ADA) — ADA 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 2r,3s,5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3IAR · 1.52 Å · ligand (2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-tetrahydro-2-(hydroxymethyl)furan-3-ol (3D1). Experimental structure, not a prediction.
What the evidence adds up to
Omenn syndrome is a rare autosomal recessive disorder that stems from severe combined immunodeficiency. It was first described by Harvard medical student Gilbert Omenn 40 years ago, and for decades its pathogenesis remained mysterious. In 2007, two separate mouse models bearing mutations in the V(D)J recombinase analogous to those causing human Omenn syndrome were shown to recapitulate the disease and provide insight into the genesis of immunodeficiency combined with autoimmunity and atopy.
The syndrome is caused by missense mutations in the recombinase activating genes. In a 2022 study of a 2-month-old boy with cough, mild anaemia, pneumonia, immunodeficiency, repeated infection, feeding difficulties, hepatomegaly, growth retardation, and heart failure, whole-exome sequencing identified a novel homozygous single nucleotide deletion (c.2662delC) in exon 2 of the RAG1 gene. This deletion leads to a frameshift and a truncated protein of 890 amino acids compared with the wildtype 1043 amino acids, making it a loss-of-function variant. The parents were heterozygous carriers, and the variant was not found in the proband’s three siblings or in 100 ethnically matched healthy controls. Karyotype and chromosomal microarray analysis found no structural abnormalities or pathogenic copy number variations.
A 2022 case report from Pakistan describes a 3-month-old child diagnosed with Omenn syndrome after being initially mistaken for other diseases. The report notes that in Omenn syndrome there is increased susceptibility to infections of the skin, lungs, and joints, as well as sepsis. Death usually ensues due to pneumonia and septicemia or septic shock. The report states that the disease can be treated by bone marrow transplantation or lymphocytic stimulation depending on the severity of the presenting immunodeficiency. No controlled trials or survival data are reported in any of these abstracts. What is still missing are prospective clinical trials with defined endpoints, larger patient cohorts to stratify by genotype and age at intervention, and dedicated funding for a disease so rare that even case series remain sparse.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Investigation · 2007 · 10 citations · open access
Murine models of Omenn syndrome
AbstractIn the 40 years since Harvard medical student Gilbert Omenn first described a rare, inherited disorder producing a paradoxical combination of immunodeficiency and immune dysregulation, the pathogenesis of Omenn syndrome (OS) has remained mysterious. In separate studies reported in this issue of the JCI, two mouse models bearing mutations in the V(D)J recombinase analogous to those causing human OS have been shown to recapitulate the disease and provide insight into the genesis of immunodeficiency combined with autoimmunity and atopy in OS and other disease settings (see the related articles beginning on pages 1260 and 1270).
Annals of Medicine and Surgery · 2022 · 8 citations · open access
An infant with omenn syndrome: A case report
AbstractBACKGROUND: Omenn syndrome is a rare, autosomal recessive disorder. It is a disorder that stems from severe combined immunodeficiency in an affected individual. The disease is also of rare occurrence in children in Pakistan because this is the age where this disease usually presents, after having developed in the child. This case report will explore all the reasons that lead to the occurrence of this syndrome while also reflecting on the management profile of the child. CASE PRESENTATION: This case report deals with the discussion of one such child who was diagnosed with Omenn Syndrome after being diagnosed with several other diseases, which were being mistaken for being the actual problem and disease, but the reality was that the child was suffering from Omenn syndrome. DISCUSSION: The child is only 3 months old and his symptoms pose a great risk to his overall health status while also making him predisposed to develop several complications and nutritional deficiencies as a result, all of which keep on adding to the burden of diseases that the child faced. In Omenn syndrome, there is an increased susceptibility to develop infections of the skin, lungs, joints, as well as sepsis. Usually, the death of the patient ensues due to pneumonia and septicemia or septic shock. CONCLUSION: Omenn syndrome is a rare disease caused by missense mutations in the recombinase activating genes. It can be treated by bone marrow transplantation or lymphocytic stimulation depending on the severity of the presenting underlying immunodeficiency.
Allergologia et Immunopathologia · 2022 · 0 citations · open access
Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome
AbstractIntroduction and objectives: Omenn syndrome (OS) is a very rare type of severe combined immunodeficiencies manifested with erythroderma, eosinophilia, hepatosplenomegaly, lymphadenopathy, and elevated level of serum IgE. OS is inherited with an autosomal recessive mode of inheritance. Germline mutations in the human RAG1 gene cause OS. Materials and methods: In this study, we investigated a 2-month-old boy with cough, mild anaemia, pneumonia, immunodeficiency, repeated infection, feeding difficulties, hepatomegaly, growth retardation, and heart failure. Parents of the proband were phenotypically normal. Results: Karyotype analysis and chromosomal microarray analysis found no chromosomal struc-tural abnormalities (46, XY) and no pathogenic copy number variations (CNVs) in the proband. Whole-exome sequencing identified a novel homozygous single nucleotide deletion (c.2662delC) in exon 2 of the RAG1 gene in the proband. Sanger sequencing confirmed that both the proband parents were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters and one elder brother of the proband and in the 100 ethnically matched normal healthy individuals. This novel homozygous deletion (c.2662delC) leads to the frameshift, which finally results in the formation of the truncated protein (p.Leu888Phefs*3) V(D)J recombination-activating protein 1 with 890 amino acids compared with the wildtype V(D)J recombination-activating protein 1 of 1043 amino acids. Hence, it is a loss-of-function variant. Conclusions: Our present study expands the mutational spectrum of the RAG1 gene associated with OS. We also strongly suggested the importance of whole-exome sequencing for the genetic screening of patients with OS.
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.
