DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for pseudohypoparathyroidism type 1A — 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 modulePseudohypoparathyroidism type 1A 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 pseudohypoparathyroidism type 1a 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
GNAS complex locus (GNAS) — GNAS 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 oladrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8WW2 · 2.79 Å · ligand OLEIC ACID (OLA). Experimental structure, not a prediction.
What the evidence adds up to
In a Tunisian family, a novel mutation in the GNAS gene was identified in adults with pseudohypoparathyroidism type 1a who presented with Fahr syndrome. The condition is defined by hypocalcaemia, hyperphosphataemia, elevated parathyroid hormone, and resistance to its biological action. A 2009 review notes that type 1 pseudohypoparathyroidism is the form clinicians most often encounter and that its diagnosis is not usually difficult, but that other types (1b, 1c, and 2) can present significant diagnostic and treatment problems despite their low prevalence.
Two late-presenting cases were reported in 2018: a 21-year-old woman with biochemical abnormalities characteristic of pseudohypoparathyroidism who had been misdiagnosed with epilepsy, and a 13-year-old boy with the classic Albright’s Hereditary Osteodystrophy phenotype (short stature, round facies, short neck, obesity, brachydactyly, subcutaneous calcifications) but without abnormalities in phospho-calcium metabolism, consistent with pseudopseudohypoparathyroidism. The authors note that although most diagnoses are made in childhood, the condition can manifest in adolescence or early adulthood.
Pseudohypoparathyroidism type 1a is caused by heterozygous inactivating mutations in the GNAS1 gene, which encodes the Gsalpha signal transducer. Patients with the Albright’s Osteodystrophy phenotype but without hormone resistance are classified as having pseudopseudohypoparathyroidism. No treatment trial, no drug repurposing data, and no quantitative outcomes such as survival or response rates appear in any of these abstracts. What is missing is any controlled clinical evidence for a specific drug intervention, a trial design that stratifies patients by mutation type or age of onset, and funding for such work.
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 Case Reports · 2022 · 3 citations · open access
Fahr syndrome discovered in adulthood revealing a rare <i>GNAS</i> mutation in pseudohypoparathyroidism type 1a in a Tunisian family
AbstractAbstract Pseudohypoparathyroidism (PHP) indicates a rare heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone (PTH), and insensitivity to the biologic activity of PTH. One of its most common types is PHP‐1a. In this report, we present a familial PHP‐1a and a novel mutation of the GNAS gene.
Problems of Endocrinology · 2009 · 1 citations · open access
Pseudohypoparathyroidism: genetic aspects
AbstractThe review of literature details the issues of genetics, the specific features of inheritance, the clinical picture and treatment of pseudohypoparathyroidisms (PHPT). In practice, clinicians more frequently deal with type 1 PHPT and the diagnosis of this type creates no significant problems. However, despite the low prevalence of the other types of PHPT - 1b, 1c, and 2, the diseases may run with noticeably clinical symptoms and present a significant problem in the context of diagnosis and treatment. This review may be of concern to both clinicians and geneticists who are interested in this problem.
Revista médica de Chile · 2018 · 1 citations · open access
Pseudohipoparatiroidismo de presentación tardía: reporte de dos casos
AbstractPseudohypoparathyroidism (PHP) is a group of rare genetic disorders that share organ targeted resistance to the action of parathyroid hormone (PTH) as a common feature. Biochemically, they may present with hypocalcemia, hyperphosphatemia and elevated PTH. Some forms present with a specific phenotype: short stature, round facies, short neck, obesity, brachydactyly and subcutaneous calcifications, called Albrigth's Hereditary Osteodystrophy (AHO). This spectrum of disorders are caused by several alterations in the gene coding for the alpha subunit of the G protein (GNAS): an ubiquitous signaling protein that mediates the action of numerous hormones such as PTH, TSH, gonadotropins, and ACTH, among others. According to their inheritance with maternal or paternal imprinting, they may manifest in a diversity of clinical forms. Although most commonly diagnosed during childhood, PHP may manifest clinically during adolescence or early adulthood. We report two late presenting cases of pseudohypoparathyroidism. A 21-year-old female with biochemical abnormalities characteristic of pseudohypoparathyroidism who was misdiagnosed as epilepsy and a 13-year-old boy with the classic AHO phenotype but without alterations in phospho-calcium metabolism, compatible with pseudopseudohypoparathyrodism.
Guthrie Journal · 1971 · 1 citations · open access
Pseudohypoparathyroidism: A Case Report
AbstractPseudohypoparathyroidism was first described by Albright and his associates in 1942 1 . It is characterized by a failure of end organ response in the kidney to parathyroid hormone. Clinically, such patients are characterized by short stature, round face, and short metacarpals; they have low serum calciums and increased serum phosphorous. In addition they may be retarded, and seizures are a frequent occurrence. Abnormal calcifications are seen on x-ray, particularly on the basal ganglion and in ligamentous structures.
[GNAS1 gene abnormality in pseudohypoparathyroidism I a].
AbstractPseudophypoparathyroidism (PHP) is characterized by hypocalcemia, hyperphosphatemia and elevated levels of parathyroid hormone (PTH) due to resistance to PTH. PHP type I a is caused by heterozygous inactivating mutation of the GNAS1 gene, which encodes signal transducer, Gsalpha. PHP type I a is associated with Albright's osteodystrophy (AHO). Those patients who have AHO phenotype without hormone resistance are affected by pseudopseudohypoparathyroidism.
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.
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