DeCure for Corticosteroid-binding globulin deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for corticosteroid-binding globulin deficiency — 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 moduleCorticosteroid-binding globulin deficiency 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 corticosteroid-binding globulin deficiency 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
serpin family A member 6 (SERPINA6) — SERPINA6 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 11alpha,14betadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2VDY · 2.3 Å · ligand (11alpha,14beta)-11,17,21-trihydroxypregn-4-ene-3,20-dione (HCY). Experimental structure, not a prediction.
What the evidence adds up to
A 2001 study of a 39-member Italian-Australian family identified a novel null mutation in the corticosteroid-binding globulin gene (c.121G-->A) that produces a premature termination codon. Among 32 family members there were 3 null homozygotes, 19 null heterozygotes, 2 compound heterozygotes, 3 Lyon heterozygotes, and 5 individuals without mutations. Plasma immunoreactive corticosteroid-binding globulin was undetectable in null homozygotes, and mean levels in null heterozygotes were reduced by approximately 50% to 18.7 ± 1.3 µg/ml (reference range 30–52 µg/ml). Morning total plasma cortisol was less than 1.8 µg/dl in homozygotes and was positively correlated with corticosteroid-binding globulin levels in heterozygotes.
Homozygotes and heterozygote null mutation subjects had a high prevalence of hypotension and fatigue. Among 19 adults with the null mutation, the systolic blood pressure z-score was 12.1 ± 3.5; 11 of 19 (54%) had a systolic blood pressure below the third percentile. The mean diastolic blood pressure z-score was 18.1 ± 3.4; 8 of 19 (42%) had a diastolic blood pressure z-score below 10. Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygotes (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome. Fatigue questionnaire scores were 25.1 ± 2.5 in 18 adults with the mutation versus 4.2 ± 1.5 in 23 healthy controls (P < 0.0001). Compound heterozygosity for both mutations resulted in plasma cortisol levels comparable to those in null homozygotes. The mechanism of the association between fatigue and relative hypotension was not established by these studies.
A 1981 review covers the physicochemical properties, biosynthesis, measurement, and physiological, pharmacological and pathological variations of human corticosteroid-binding globulin, with particular emphasis on pregnancy and oral contraceptives. A 1987 article on problems when withdrawing corticosteroids notes that prolonged treatment with doses above 5–7.5 mg prednisolone daily can suppress the hypothalamo-pituitary-adrenal axis, and that disease relapse is the commonest difficulty during or after withdrawal.
What is still missing: no treatment trial has been conducted for corticosteroid-binding globulin deficiency. The 2001 study did not establish a causal mechanism linking the mutation to fatigue and hypotension. There is no data on whether cortisol replacement alters symptoms in these patients, and no validated patient stratification beyond mutation status. Funding for a controlled trial of physiological hormone replacement in this rare condition has not been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Endocrinology · 1981 · 188 citations · open access
HUMAN CORTICOSTEROID BINDING GLOBULIN
AbstractThe literature on corticosteroid binding globulin (transcortin) in the human is reviewed under the following headings: physicochemical properties, biosynthesis, measurement, and physiological, pharmacological and pathological variations with particular emphasis of the effects of pregnancy and oral contraceptives. Finally, the physiological implications of corticosteroid binding globulin are discussed.
The Journal of Clinical Endocrinology & Metabolism · 2001 · 101 citations · open access
Familial Corticosteroid-Binding Globulin Deficiency Due to a Novel Null Mutation: Association with Fatigue and Relative Hypotension
AbstractCorticosteroid-binding globulin is a 383-amino acid glycoprotein that serves a hormone transport role and may have functions related to the stress response and inflammation. We describe a 39-member Italian-Australian family with a novel complete loss of function (null) mutation of the corticosteroid-binding globulin gene. A second, previously described, mutation (Lyon) segregated independently in the same kindred. The novel exon 2 mutation led to a premature termination codon corresponding to residue -12 of the procorticosteroid-binding globulin molecule (c.121G-->A). Among 32 family members there were 3 null homozygotes, 19 null heterozygotes, 2 compound heterozygotes, 3 Lyon heterozygotes, and 5 individuals without corticosteroid-binding globulin mutations. Plasma immunoreactive corticosteroid-binding globulin was undetectable in null homozygotes, and mean corticosteroid-binding globulin levels were reduced by approximately 50% at 18.7 +/- 1.3 microg/ml (reference range, 30-52 microg/ml) in null heterozygotes. Morning total plasma cortisol levels were less than 1.8 microg/dl in homozygotes and were positively correlated to the plasma corticosteroid-binding globulin level in heterozygotes. Homozygotes and heterozygote null mutation subjects had a high prevalence of hypotension and fatigue. Among 19 adults with the null mutation, the systolic blood pressure z-score was 12.1 +/- 3.5; 11 of 19 subjects (54%) had a systolic blood pressure below the third percentile. The mean diastolic blood pressure z-score was 18.1 +/- 3.4; 8 of 19 subjects (42%) had a diastolic blood pressure z-score below 10. Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygote subjects (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome. Fatigue questionnaires revealed scores of 25.1 +/- 2.5 in 18 adults with the mutation vs. 4.2 +/- 1.5 in 23 healthy controls (P < 0.0001). Compound heterozygosity for both mutations resulted in plasma cortisol levels comparable to those in null homozygotes. Abnormal corticosteroid-binding globulin concentrations or binding affinity may lead to the misdiagnosis of isolated ACTH deficiency. The mechanism of the association between fatigue and relative hypotension is not established by these studies. As idiopathic fatigue disorders are associated with relatively low plasma cortisol, abnormalities of corticosteroid-binding globulin may be pathogenic.
Drug and Therapeutics Bulletin · 1987 · 2 citations
Problems when withdrawing corticosteroids
AbstractProlonged treatment with a corticosteroid, unless to replace hormone deficiency, carries well recognised risks which include hypertension, hyperglycaemia, osteoporosis and cushingoid appearance. Moreover, doses above 5–7.5mg prednisolone daily can suppress the hypothalamo-pituitary-adrenal (HPA) axis. Needlessly high doses should therefore be avoided and treatment should be withdrawn when it is no longer needed. Many unwanted effects then disappear or cease to progress - though osteoporosis may persist and the child whose growth has been suppressed may not fully catch up. Disease relapse is the commonest difficulty during or following withdrawal of corticosteroid treatment. This article discusses some other problems that may arise.
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.
