DeCure for Secondary hyperparathyroidism of renal origin
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for secondary hyperparathyroidism of renal origin — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSecondary hyperparathyroidism of renal origin maps to a 14-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 secondary hyperparathyroidism of renal origin 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
apolipoprotein L1 (APOL1) — APOL1 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 eohdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7LF7 · 2.026 Å · ligand ETHANOL (EOH). Experimental structure, not a prediction.
What the evidence adds up to
Secondary hyperparathyroidism of renal origin is a metabolic state in which the parathyroid glands produce an excessive but not autonomous amount of parathyroid hormone, encountered invariably in chronic renal failure and in other disease states where there is resistance to the metabolic actions of the hormone. This resistance leads, through mechanisms as yet unclarified, to hyperplasia of the parathyroids. Postmortem studies of patients with renal failure have shown hyperplastic parathyroids and changes typical of osteitis fibrosa in many with far advanced renal failure. Radioimmunoassay studies have confirmed increased concentration of parathyroid hormone in these patients.
In chronic kidney disease patients, secondary hyperparathyroidism is reported to increase both morbidity and mortality, especially cardiovascular. Difficulty in treatment in clinical practice frequently arises from inadequate conduct by clinicians and common non-compliance to therapy by patients, with particular attention needed to dialysis features, nutritional habits, and medical therapy. The American Association of Endocrine Surgeons published evidence-based guidelines in 2022 for the definitive surgical management of secondary and tertiary renal hyperparathyroidism, covering epidemiology, pathophysiology, preoperative and perioperative care, surgical planning and parathyroidectomy, adjuncts and approaches, outcomes, and reoperation. These guidelines were constructed by a panel of 10 experts reviewing medical literature from 1985 to 2021, using the American College of Physicians grading system, and were reviewed by the Association membership.
Research using novel genetically modified mouse models and clinical data from 106 healthcare organisations has revealed intricate connections between mTORC1 activity, parathyroid gland structure, and the response to chronic kidney disease. Previous research demonstrated activation of the parathyroid mTORC1 pathway in CKD-related secondary hyperparathyroidism. Despite this, the underlying causes of CKD-related secondary hyperparathyroidism and the related parathyroid signalling pathways remain elusive.
What is still missing is a clear understanding of the signalling pathways that drive parathyroid hyperplasia in chronic kidney disease, as well as consistent patient adherence to therapy and clinician adherence to treatment protocols. No randomised trial data are presented that compare medical versus surgical approaches in a controlled fashion, and no specific drug therapy is evaluated in these abstracts. The evidence base for surgical guidelines relies on expert consensus and literature review rather than prospective trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Surgery · 2022 · 116 citations
The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Secondary and Tertiary Renal Hyperparathyroidism
AbstractOBJECTIVE: To develop evidence-based recommendations for safe, effective, and appropriate treatment of secondary (SHPT) and tertiary (THPT) renal hyperparathyroidism. BACKGROUND: Hyperparathyroidism is common among patients with chronic kidney disease, end-stage kidney disease, and kidney transplant. The surgical management of SHPT and THPT is nuanced and requires a multidisciplinary approach. There are currently no clinical practice guidelines that address the surgical treatment of SHPT and THPT. METHODS: Medical literature was reviewed from January 1, 1985 to present January 1, 2021 by a panel of 10 experts in SHPT and THPT. Recommendations using the best available evidence was constructed. The American College of Physicians grading system was used to determine levels of evidence. Recommendations were discussed to consensus. The American Association of Endocrine Surgeons membership reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines present the epidemiology and pathophysiology of SHPT and THPT and provide recommendations for work-up and management of SHPT and THPT for all involved clinicians. It outlines the preoperative, intraoperative, and postoperative management of SHPT and THPT, as well as related definitions, operative techniques, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Preoperative and Perioperative Care, Surgical Planning and Parathyroidectomy, Adjuncts and Approaches, Outcomes, and Reoperation. CONCLUSIONS: Evidence-based guidelines were created to assist clinicians in the optimal management of secondary and tertiary renal hyperparathyroidism.
Archives of Internal Medicine · 1969 · 63 citations
Secondary Hyperparathyroidism in Chronic Renal Disease
AbstractSecondary hyperparathyroidism is a metabolic state characterized by an excessive but not autonomous rate of production of parathyroid hormone: this disorder is encountered invariably in chronic renal failure and also in other disease states where there is resistance to the metabolic actions of parathyroid hormone.<sup>1</sup>The resistance to the biological effects of the hormone lead, through mechanisms as yet unclarified, to hyperplasia of the parathyroids. For many years secondary hyperparathyroidism had been postulated to be present in patients with chronic renal disease.<sup>2</sup>It was known from postmortem studies of patients with renal failure that the parathyroids were hyperplastic; in addition, changes typical of osteitis fibrosa were found in many patients with far advanced renal failure, as discussed elsewhere in this symposium by Stanbury and others. Studies with the radioimmunoassay by Berson and Yalow, Reiss (reviewed in this symposium), and us have now confirmed that there is an increased concentration of
The Importance of Adherence in the Treatment of Secondary Hyperparathyroidism
AbstractSecondary hyperparathyroidism (SHPT) is a frequent condition in the presence of chronic kidney disease (CKD). In CKD patients, SHPT is reported to increase both morbidity and mortality, especially cardiovascular. The difficulty in the treatment of SHPT in clinical practice is frequently encountered from a not always adequate conduct of the clinicians and a common non-compliance to the therapy of CKD patients. In this review, the greatest difficulties from clinicians and CKD-patients' point of view in the treatment of SHPT will be addressed, with particular attention to those related to dialysis features, nutritional habits, and medical therapy.
Archives of Internal Medicine · 1969 · 9 citations
Secondary hyperparathyroidism in chronic renal disease
AbstractSecondary hyperparathyroidism is a metabolic state characterized by an excessive but not autonomous rate of production of parathyroid hormone: this disorder is encountered invariably in chronic renal failure and also in other disease states where there is resistance to the metabolic actions of parathyroid hormone.<sup>1</sup>The resistance to the biological effects of the hormone lead, through mechanisms as yet unclarified, to hyperplasia of the parathyroids. For many years secondary hyperparathyroidism had been postulated to be present in patients with chronic renal disease.<sup>2</sup>It was known from postmortem studies of patients with renal failure that the parathyroids were hyperplastic; in addition, changes typical of osteitis fibrosa were found in many patients with far advanced renal failure, as discussed elsewhere in this symposium by Stanbury and others. Studies with the radioimmunoassay by Berson and Yalow, Reiss (reviewed in this symposium), and us have now confirmed that there is an increased concentration of
Kidney International Reports · 2024 · 0 citations · open access
WCN24-1536 mTORC1 is central for parathyroid gland integrity and CKD induced secondary hyperparathyroidism: Insights from genetic mouse models and clinical data
AbstractSecondary hyperparathyroidism (SHP) associated with chronic kidney disease (CKD) represents a significant health concern, contributing to morbidity and mortality. Despite its clinical importance, the underlying causes of CKD-SHP and the related parathyroid signaling pathways remain elusive. Our previous research demonstrated the activation of the parathyroid mTORC1 pathway in CKDSHP. Utilizing novel genetically modified mouse models and clinical data from 106 healthcare organizations, we reveal intricate connections between mTORC1 activity, parathyroid gland structure, and the response to CKD.
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.
