DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant hypocalcemia — 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 moduleAutosomal dominant hypocalcemia 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 autosomal dominant hypocalcemia 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
calcium sensing receptor (CASR) — CASR 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 trpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7DTV · 3.5 Å · ligand TRYPTOPHAN (TRP). Experimental structure, not a prediction.
What the evidence adds up to
A 2006 case report describes an infant who presented with hypocalcemia at three weeks of age and was found to have a de novo missense mutation (L727Q) in the calcium-sensing receptor gene. When the mutant receptor was expressed in a cell line, it showed a leftward shift in its dose-response curve compared to the wild-type receptor (EC50 2.59 ± 0.11 mM vs 3.78 ± 0.12 mM, p < 0.001), meaning it was more sensitive to calcium. The child was treated with twice-daily recombinant human PTH(1-34) for 17 months. During that period, no further serious hypocalcemic episodes occurred, and urinary calcium excretion declined remarkably. The authors concluded that PTH should be evaluated further as a treatment for autosomal dominant hypocalcemia in young patients.
A 2022 case study and literature review by Wu et al. also addresses autosomal dominant hypocalcemia with a novel CASR mutation, but the abstract provided contains no data on treatment outcomes, patient numbers, or response rates. It is a supplemental material file with no clinical results reported in the available text.
The 2006 report is limited to a single infant. No controlled trial, no comparison group, and no long-term follow-up beyond 17 months are described. The 2022 publication offers no additional evidence on treatment efficacy.
What is still missing: a prospective trial with a sufficient number of patients, standardised outcome measures for hypocalcemic episodes and renal function, and stratification by age and specific CASR mutation type. Without these, the role of PTH in this rare disorder remains unproven.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Clinical Endocrinology & Metabolism · 2006 · 54 citations · open access
A Hypocalcemic Child with a Novel Activating Mutation of the Calcium-Sensing Receptor Gene: Successful Treatment with Recombinant Human Parathyroid Hormone
AbstractCONTEXT: Persistent hypercalciuria, with the attendant risk of nephrocalcinosis and eventual renal failure, is common in hypoparathyroid patients, especially those with activating mutations of the calcium-sensing receptor (CASR) gene, being treated with oral calcium and calcitriol. Treatment with replacement PTH may be warranted, although this has yet to be evaluated in children. OBJECTIVES: The objectives of this study were to identify the cause of the disorder in a young hypocalcemic patient and to assess the efficacy of treatment of the patient with recombinant human PTH(1-34). SUBJECT: An infant presenting with hypocalcemia at 3 wk of age was studied. METHODS: CASR gene mutation analysis was performed on genomic DNA of the proband and family members. The patient was treated with twice-daily administration of recombinant human PTH(1-34) over a 17-month period. RESULTS: The proband was heterozygous for a de novo novel missense mutation (L727Q), on the border between transmembrane helix 4 and intracellular loop 2 of the CASR. When transiently expressed in a human embryonic kidney 293 cell line, the mutant receptor demonstrated a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve vs. that for the wild-type receptor [EC(50); mutant, 2.59 +/- 0.11 mm (mean +/- se) vs. wild-type, 3.78 +/- 0.12 mm, P < 0.001]. During treatment with PTH(1-34), the patient had no further serious hypocalcemic episodes, and his urinary calcium excretion declined remarkably. CONCLUSION: PTH should be evaluated further as a treatment of autosomal dominant hypocalcemia in young patients.
Sage Journals Data · 2022 · 0 citations · open access
sj-pdf-2-imr-10.1177_03000605221110489 - Supplemental material for Autosomal dominant hypocalcemia with a novel <i>CASR</i> mutation: a case study and literature review
AbstractSupplemental material, sj-pdf-2-imr-10.1177_03000605221110489 for Autosomal dominant hypocalcemia with a novel <i>CASR</i> mutation: a case study and literature review by Yingying Wu, Chao Zhang, Xiaojun Huang, Li Cao, Shihua Liu and Ping Zhong in Journal of International Medical Research
sj-pdf-2-imr-10.1177_03000605221110489 - Supplemental material for Autosomal dominant hypocalcemia with a novel <i>CASR</i> mutation: a case study and literature review
AbstractSupplemental material, sj-pdf-2-imr-10.1177_03000605221110489 for Autosomal dominant hypocalcemia with a novel <i>CASR</i> mutation: a case study and literature review by Yingying Wu, Chao Zhang, Xiaojun Huang, Li Cao, Shihua Liu and Ping Zhong in Journal of International Medical Research
sj-pdf-1-imr-10.1177_03000605221110489 - Supplemental material for Autosomal dominant hypocalcemia with a novel <i>CASR</i> mutation: a case study and literature review
AbstractSupplemental material, sj-pdf-1-imr-10.1177_03000605221110489 for Autosomal dominant hypocalcemia with a novel <i>CASR</i> mutation: a case study and literature review by Yingying Wu, Chao Zhang, Xiaojun Huang, Li Cao, Shihua Liu and Ping Zhong in Journal of International Medical Research
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.
