DeCure for Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant — 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 moduleGrowth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant 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 growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant 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
signal transducer and activator of transcription 5B (STAT5B) — STAT5B 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 6MBZ · 3.21 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Two male siblings with a homozygous STAT5B frameshift mutation (p.L142fsX161) presented with growth hormone insensitivity syndrome, hyperprolactinemia, atopic eczema, interstitial lung disease, and thrombocytopenic purpura. Lymphopenia and reduced natural killer cell counts were observed, without immunoglobulin abnormalities. The younger sibling, aged 9.9 years, received recombinant human IGF1 (rhIGF1) at 110 µg/kg twice daily for 1.5 years. His growth velocity changed from 2.3 to 3.0 cm per year, which the authors describe as no significant change. They note that chronic illness may have contributed to the poor result.
A separate 2007 report describes a patient with Laron syndrome caused by a homozygous TT insertion at nucleotide 422 in exon 5 of the growth hormone receptor gene, leading to a truncated receptor. That abstract provides no data on treatment response or immune function. An older 1981 report describes a family with isolated growth hormone deficiency inherited in an autosomal dominant pattern, but it does not involve STAT5B, GHR mutations, or immune dysregulation.
No abstract in this set reports a successful treatment for growth hormone insensitivity syndrome with immune dysregulation 2. The only treatment data come from the two siblings with the STAT5B mutation, and the response to rhIGF1 was negligible. What is missing are prospective trials with adequate sample sizes, longer treatment durations, and stratification by underlying mutation type and presence of chronic lung disease. No funding source or planned trial is mentioned in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Endocrinology · 2010 · 63 citations · open access
A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings
AbstractBACKGROUND: GH insensitivity (GHI) syndrome caused by STAT5B mutations was recently reported, and it is characterized by extreme short stature and immune dysfunction. Treatment with recombinant human IGF1 (rhIGF1) is approved for patients with GHI, but the growth response to this therapy in patients with STAT5B mutations has not been reported. OBJECTIVES: To report the clinical features, molecular findings, and the short-term growth response to rhIGF1 therapy in patients with STAT5B mutation. SUBJECTS AND METHODS: Hormonal and immunological evaluations were performed in two male siblings with GHI associated with atopic eczema, interstitial lung disease, and thrombocytopenic purpura. STAT5B genes were directly sequenced. The younger sibling was treated with rhIGF1 at a dose of 110 microg/kg BID. RESULTS: Both siblings had laboratory findings compatible with GHI associated with hyperprolactinemia. Lymphopenia and reduced number of natural killer cells without immunoglobulin abnormalities were observed. STAT5B sequence revealed a homozygous frameshift mutation (p.L142fsX161) in both siblings. The younger sibling (9.9 years of age) was treated with rhIGF1 at appropriate dosage, and he did not present any significant change in his growth velocity (from 2.3 to 3.0 cm/year after 1.5 years of therapy). The presence of a chronic illness could possibly be responsible for the poor result of rhIGF1 treatment. Further studies in patients with STAT5B defects are necessary to define the response to rhIGF1 treatment in this disorder. CONCLUSION: GHI associated with immune dysfunction, especially interstitial lung disease, and hyperprolactinemia is strongly suggestive of a mutation in STAT5B in both sexes.
Journal of Pediatric Endocrinology and Metabolism · 2007 · 13 citations
Identification of a Novel Mutation in the Human Growth Hormone Receptor Gene (GHR) in a Patient with Laron Syndrome
AbstractDeletions and mutations in the growth hormone receptor (GHR) gene are the underlying etiology of Laron syndrome (LS) or growth hormone (GH) insensitivity syndrome (GHIS), an autosomal recessive disease. Most patients are distributed in or originate from Mediterranean and Middle-Eastern countries. Sixty mutations have been described so far. We report a novel mutation in the GHR gene in a patient with LS. Genomic DNA sequencing of exon 5 revealed a TT insertion at nucleotide 422 after codon 122. The insertion resulted in a frameshift introducing a premature termination codon that led to a truncated receptor. We present clinical, biochemical and molecular evidence of LS as the result of this homozygous insertion.
AbstractA family is reported with isolated growth hormone deficiency in two children, their mother and, presumably, also in two maternal uncles and their maternal grandmother. Autosomal dominant inheritance is the best explanation. Isolated growth hormone deficiency is apparently a heterogeneous condition, including autosomal dominant, autosomal recessive as well as non-genetic diseases.
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.
