DeCure for Pigmented nodular adrenocortical disease, primary, 3
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for pigmented nodular adrenocortical disease, primary, 3 — 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 modulePigmented nodular adrenocortical disease, primary, 3 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 pigmented nodular adrenocortical disease, primary, 3 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.
What the evidence adds up to
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare bilateral adrenocortical hyperplasia that causes ACTH-independent Cushing syndrome. The adrenal glands are small to normal-sized and contain multiple small cortical pigmented nodules. PPNAD can occur in isolation or as part of Carney complex, a multiple neoplasia syndrome in which Cushing syndrome is the most common endocrine manifestation. A 1999 study described a paradoxical increase in cortisol after dexamethasone administration as a diagnostic feature of PPNAD, but that study did not test any drug treatment.
In 2010, four patients aged 10 to 38 years with Cushing syndrome and germline inactivating mutations of PDE11A4 were described. Three of the four, including a mother and daughter, had PPNAD pathology identical to that caused by PRKAR1A mutations. Their adrenal glands were small with deep pigmented micronodules. The fourth patient had slightly enlarged glands with diffuse superficial cortex hyperplasia extending into epi-adrenal fat. No treatment or drug response was reported in these patients.
All identified molecular defects in PPNAD involve the cAMP signalling pathway. PDE11A4 encodes a phosphodiesterase that hydrolyses cyclic AMP and cyclic GMP in the adrenal cortex. No drug that targets this pathway has been tested in PPNAD patients in any of the provided abstracts. The 2007 review notes that molecular genetics and diagnostic tools have advanced, but it does not describe any pharmacological intervention.
What is missing: no clinical trial has tested a phosphodiesterase inhibitor or any other drug in PPNAD patients. There is no data on whether targeting cAMP signalling would reduce cortisol production or shrink nodules. The rarity of the disease makes trial recruitment difficult, and no funding for a repurposing trial is mentioned in these abstracts. Patient stratification by specific gene mutation (PDE11A4 versus PRKAR1A) has not been attempted in a treatment context.
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 American Journal of Surgical Pathology · 2010 · 36 citations · open access
Familial Micronodular Adrenocortical Disease, Cushing Syndrome, and Mutations of the Gene Encoding Phosphodiesterase 11A4 (PDE11A)
AbstractWe present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat.
Arquivos Brasileiros de Endocrinologia & Metabologia · 2007 · 31 citations · open access
Primary pigmented nodular adrenocortical disease and Cushing's syndrome
AbstractPrimary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with corticotrophin (ACTH)-independent Cushing's syndrome (CS) and is characterized by small to normal-sized adrenal glands containing multiple small cortical pigmented nodules (1,2). PPNAD may occur in an isolated form or associated with a multiple neoplasia syndrome, the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, or Carney complex, in which Cushing's syndrome is the most common endocrine manifestation (3). Molecular studies have led to the identification of several genes, defects in which may predispose PPNAD formation; all of these molecules play important role for the cAMP signaling pathway. This review intends to present the most recent knowledge of the pathology and molecular genetics of the benign bilateral adrenocortical lesions, as well as to discuss the modern tools for diagnostics and treatment of this condition.
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.
