DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Donohue syndrome — 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 moduleDonohue syndrome 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 donohue 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
insulin receptor (INSR) — INSR 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 8U4C · 3.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Donohue syndrome is a rare autosomal recessive disorder caused by homozygous or compound heterozygous mutations in the insulin receptor gene INSR. One case report describes an Arab male born at 37 weeks to consanguineous parents, with severe intrauterine growth restriction, dysmorphic features, hyperinsulinism, increased C-peptide, thrombocytopenia, leucopenia, and anaemia. Diagnosis was based on clinical features and genetic analysis via PCR and sequencing of INSR. The abstract states that treatment with recombinant insulin-like growth factor 1 demonstrates effectiveness, and that combination treatment with insulin-like growth factor binding protein 3 resulted in an increased lifespan, but provides no numerical data on survival or response rates.
A second report describes a Tunisian patient born at 37 weeks to unrelated parents, with intrauterine growth retardation, nipple hypertrophy, macropenis, distended abdomen, hirsutism, and dysmorphic features. The clinical course included failure to thrive, alternating hypoglycaemia and hyperglycaemia, and direct hyperbilirubinaemia. A homozygous nonsense mutation c.2270 C>T (Arg924X) in exon 14 of INSR was identified. The patient developed enterocolitis and died at 3 months old. No treatment was reported to alter this outcome.
A third report describes a 14-year-old girl with consanguineous parents, presenting with polydipsia, polyphagia, weight loss, elfin face, distended abdomen, enlarged clitoris, hypertrichosis, acanthosis nigricans, and a patent ductus arteriosus. She had hyperglycaemia and hyperinsulinism. The abstract notes that most patients with Donohue syndrome die prematurely, and that this child’s longer survival may represent a milder form of the disorder. No treatment or survival data beyond the case description are provided.
Across these reports, no controlled trial data exist. The evidence is limited to three single-case descriptions, one of which reports death at three months. The claim that recombinant insulin-like growth factor 1 with binding protein 3 increases lifespan is not supported by any quantitative survival data in the abstracts. What is missing is any systematic trial, any patient stratification by mutation type, and any funding for prospective natural history or treatment studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Medicine · 2016 · 18 citations · open access
Classic Case Report of Donohue Syndrome (Leprechaunism; OMIM *246200)
AbstractDonohue syndrome ([DS]; leprechaunism) describes a genetic autosomal recessive disorder that results from the presence of homozygous or compound heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2).Donohue syndrome is associated with a fatal congenital form of dwarfism with features of intrauterine and postnatal growth retardation, exaggerated hyperglycemia with hyperinsulinism and dysmorphic abnormalities.We present a case of DS owing to the rarity of this syndrome (1 case in every million births). We discuss how the disease presents, its genetic underpinning, and its prevention.The case was encountered in an Arab male born on 1 September, 2014, for consanguineous parents. The delivery was via cesarean section at 37 weeks gestation due to severe intrauterine growth restriction and nonprogress labor term. The patient was admitted to the Neonatal Intensive Care Unit due to infection, and jaundice. Dysmorphic features, abnormalities of the craniofacial region, low birth weight, skin abnormalities, abdominal distension and hypertrichosis were observed. Laboratory examinations showed, hyperinsulinism, increased C-peptide, thrombocytopenia, leucopenia, and anemia.The diagnosis of DS was done based on the combinations of typical dysmorphic characteristics, clinical evaluation, supported by genetic analysis and exaggerated biochemical results. Genetic diagnosis of DS was performed through analysis of DNA via polymerase chain reaction (PCR). A qualitative real-time PCR was used, to monitor the amplification of a targeted DNA molecule during the PCR. Other technique using sequencing of the INSR gene, which permits genetic diagnosis, counseling, and antenatal diagnoses in subsequent pregnancies, were also performed.Treatment of DS is supportive and requires the combined efforts of a multidisciplinary team, which include pediatricians, endocrinologists, dermatologists, and other health care professionals. Currently, treatment with recombinant insulin-like growth factor 1 demonstrates effectiveness, and a combination treatment with insulin-like growth factor binding protein 3 resulted in an increased lifespan.There is a scarcity of genetic information on DS among the Arab population. Consanguinity is one of underlying reasons for the appearance of rare genetic disorders. Inbreeding has long been considered a controversial phenomenon. Genetic counseling and overwhelming the alertness of the negative consequences of consanguinity on public health are warranted.
Journal of Pediatric Endocrinology and Metabolism · 2016 · 6 citations
Arg924X homozygous mutation in insulin receptor gene in a Tunisian patient with Donohue syndrome
AbstractDonohue syndrome (DS) is a rare and lethal autosomal recessive disease caused by mutations in the insulin receptor (INSR) gene, manifesting marked insulin resistance, severe growth retardation, hypertrichosis, and characteristic dysmorphic features. We describe a new case of Donohue syndrome born at 37 weeks' gestation of unrelated parents and presented with intra-uterine growth retardation, nipple hypertrophy, macropenis, distended abdomen, hirsutism and dysmorphic features. The clinical course showed failure to thrive, and episodes of alternating hypoglycemia and hyperglycemia. Laboratory tests revealed direct hyperbilirubinemia. The diagnosis of Donohue syndrome was established based on the above clinical characteristics and determination of the INSR mutation. He was found to have homozygous nonsense mutation c. 2270 C>T (Arg924X) at exon 14 of the INSR gene. He later developed enterocolitis and died at 3 months old. Prenatal diagnosis was performed for the family via chorionic villous biopsy. We try to explain gastrointestinal dysfunction seen in our patient.
A Syndrome of Insulin Resistance Resembling Donohue Syndrome with Patent Ductus Arteriosus
AbstractDonohue syndrome, a rare autosomal recessive disorder, is associated with the mutation of the insulin receptor gene in the short arm of the 19th chromosome. It is very rare that a syndrome of insulin resistance resembles Donohue syndrome with patent ductus arteriosus. A 14-year-old girl, whose parents were consanguineous, was often admitted for abdominal pain over the past 8 years. She presented not only polydipsia, polyphagia, and weight loss but also small elfin face, distended abdomen, enlarged clitoris, hypertrichosis, acanthosis nigricans of the neck, decreased subcutaneous fat and 3/6 continuous murmur radiating to the right shoulder with thrill on 2nd to 3rd left sternal border. In addition, she had hyperglycemia, hyperinsulinism, and patent ductus arteriosus by laboratory examination and echocardiography, respectively. This child shows insulin resistance resembling Donohue syndrome with patent ductus arteriosus. Most of patients with Donohue syndrome die prematurely. The child surviving for a long time may have a milder form of Donohue syndrome and may be due to a less severe form of the defective gene. Chromosomal abnormalities may be also associated with this disease.
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.
