Rare & Orphan Lab · DeCure for X
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Carney complex — 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.
No approved-drug candidate for carney complex 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.
protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) — PRKAR1A 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.
RCSB Protein Data Bank · entry 5KJZ · 1.347 Å · ligand CYCLIC GUANOSINE MONOPHOSPHATE (PCG). Experimental structure, not a prediction.
Carney complex is a rare autosomal dominant genetic disorder characterised by multiple neoplasias affecting endocrine organs, including pigmented micronodular adrenal dysplasia, cardiac and skin myyxomas, lentiginosis, giant cell sertoliomas, and acromegaly. A few hundred patients have been described worldwide. Familial pattern occurs in roughly half of patients. The disease is caused by gain-of-function mutations in the regulatory subunits of cAMP-dependent protein kinase (PKA). In Carney complex patients, basal PKA activity is high even in the absence of cAMP because PKA is not tightly regulated. This contrasts with acrodysostosis, where mutations in the same RIa gene produce a loss-of-function phenotype and the holoenzyme is more difficult to activate.
The 2015 and 2012 reviews describe medical and surgical management but provide no trial data, no response rates, and no survival figures. The 2010 report presents three first-degree relatives within one family but again gives no quantitative outcomes. The 2024 review calls for a thorough exploration of pathophysiology to guide early diagnosis and management, but it does not report any new treatment results or controlled studies.
No drug is mentioned in any of these abstracts. There is no evidence from randomised trials, no reported response to any pharmacological agent, and no survival data. The only mechanistic finding is that PKA activity is constitutively high in Carney complex, which suggests a potential target, but no intervention has been tested in patients.
What is missing is any clinical trial of a PKA inhibitor or any other drug in Carney complex patients. There are no prospective studies, no stratified patient cohorts, and no funding commitments for such trials. The rarity of the disease makes recruitment difficult, and no validated endpoints exist for this multisystem disorder.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractCarney complex is a rare, autosomal dominant genetic disorder that consists of multiple myxomatous lesions and endocrine abnormalities, including skin lesions, cardiac myxomas, primary pigmented nodular adrenocortical disease, and acromegaly. This review discusses the medical and surgical treatment of patients with Carney complex.
https://doi.org/10.1111/jocs.12575AbstractCarney complex is a rare hereditary syndrome characterized by an autosomal-dominant mode of inheritance and associated with multiple neoplasias affecting endocrine organs. The typical manifestations of this syndrome include pigmented micronodular adrenal dysplasia, lentiginosis, heart and skin myxomas, giant cell sertoliomas, and some other neoplasias. To date, a few hundred patients with this pathology have been described worldwide. A review of the available data about Carney complex is presented.
https://doi.org/10.14341/probl201258322-30AbstractThe Carney complex, the first reported in a series of 40 patients by J. A. Carney in 1985, is an autosomal dominant disease that is characterized by multiple neoplasia. The disease has a familial pattern in approximately one-half of the patients. We present the three cases of the Carney complex within one family.
https://doi.org/10.3348/jksr.2010.62.4.393AbstractAlthough cAMP‐dependent protein kinase (PKA) was the second regulatory protein kinase to be discovered, it was the first to be crystallized and has served ever since as a prototype for the large and diverse protein kinase superfamily. PKA, ubiquitous in mammalian cells, is a critical signaling node and regulates a plethora of biological processes. Unlike most protein kinases, which are regulated by turnover of an activation loop phosphate, PKA is synthesized as a stable phosphoprotein and then assembled as an inhibited holoenzyme complex with two cAMP‐controlled and functionally non‐redundant regulatory (R) subunits (RIa, RIb, RIIa, RIIb). Although each inactive R 2 C‐ 2 holoenzyme consists of an R‐subunit dimer and two catalytic (C) subunits, the quaternary structures of each R 2 C 2 holoenzyme are remarkably different indicating unique but overlapping pathways for allosteric regulation. There are many recently discovered autosomal dominant mutations in PKA signaling that are directly linked to disease phenotyes, and these can be classified into distinct categories. Cushings Disease and Carney Complex (CNC) Disease are caused by gain‐of‐function mutations in the catalytic and regulatory subunits, respectively. A number of single mutations in either subunit lead to a phenotype where PKA activity is not tightly regulated. In these patients the basal PKA activity levels are high even in the absence of cAMP. In contrast, hormone resistance and lowered PKA activity was observed in acrodysostosis (ACRDYS) patients, a disease that is associated with severe skeletal defects. Developmental delay and intellectual disability also accompany ACRDYS patients. ACRDYS1 patients harbor mutations in the RIa gene but these patients, in contrast to CNC patients, have a loss‐of‐function phenotype; the RIa holoenzyme is more difficult to activate. Perhaps the most striking PKA‐linked disease mutation so far is a fusion protein between DNAJB1 and the PKA Ca subunit, which was discovered to be a driver of a childhood liver cancer, fibrolamellar hepatocellular carcinoma (FLHCC). In other cases, inhibition of PKA can lead to an invasive phenotype suggesting that PKA can function as both a tumor driver and a tumor suppressor. Recently, a point mutation in the RIb dimerization/docking domain was found in patients diagnosed with a neurodegenerative disease. This mutation disrupts dimerization, prevents AKAP binding and thus abolishes targeting even though the residual activity of the complex is robustly regulated by cAMP. The variety of mutations that lead to dysfunctional PKA signaling is consistent with its central role in regulating so many biological events. The consequences of dysfunctional PKA signaling will be both diverse and cell‐specific. Support or Funding Information Funding for this research was from GM34921 to sst and GM100310 to gv
https://doi.org/10.1096/fasebj.30.1_supplement.510.3AbstractCarney Complex (CNC) is a rare, complex, and multisystem disorder with variable clinical manifestations, characterized by the development of benign tumors and hyperplastic lesions in several organ systems. This article provides a comprehensive overview of CNC, encompassing its clinical features, genetic underpinnings, and current therapeutic interventions. With an emphasis on the diverse clinical presentations and challenges associated with this condition, the aim of this review is to enhance our understanding of CNC, shed light on the latest research findings, and explore potential directions for future studies. A thorough exploration of the pathophysiology of CNC is essential to guide early diagnosis, management, and improved patient outcomes.
https://doi.org/10.5281/zenodo.10464616Disease 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.
