DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for hyperparathyroidism — screening already-approved drugs against its 29-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHyperparathyroidism maps to a 29-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
approvedAlfacalcidolVitamin D receptor agonist
Structures already discussed alongside hyperparathyroidism in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of CYP124 — Alfacalcidol has a real, experimentally solved structure in complex with this target (PDB 6T0H, 1.18 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet m9bdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6T0H · 1.18 Å · ligand Alfacalcidol (M9B). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective cohort of 74 patients with primary hyperparathyroidism, surgical treatment that normalised calcium levels produced statistically significant improvements in health-related quality of life measured by the SF-36 at one year. Before surgery the group was significantly impaired in five of eight domains compared with national norms; after surgery the group was nearly indistinguishable from the norm. Patients referred as asymptomatic showed significant preoperative impairment in three domains and significant improvement in two, while symptomatic patients showed impairment and improvement in seven domains. The study did not include a non-surgical control group.
A 2017 systematic review of medical management for primary hyperparathyroidism analysed 54 studies. Weighted mean reductions in serum total calcium from baseline were 0.31 mmol/L for pamidronate, 0.07 for alendronate, 0.20 for clodronate, 0.16 for mixed bisphosphonates, and 0.37 for cinacalcet. The effect of bisphosphonates on serum calcium decreased significantly over time, whereas cinacalcet maintained its effect. Bisphosphonates improved bone mineral density; cinacalcet did not. The review noted that combining resorptive agents with calcimimetics could be rewarding but called for more studies. No drug has been shown to alter hard endpoints such as survival or fracture rates in primary hyperparathyroidism.
Parathyroid carcinoma accounts for less than 1% of primary hyperparathyroidism cases and is often not diagnosed before surgery. A 2014 case report describes a 29-year-old man whose carcinoma was found only at neck exploration after a pathologic fracture; the initial operation offered the best chance for cure. Familial forms of primary hyperparathyroidism have been described, and several responsible genes have been identified, but the 2004 review notes that mutational analysis has not yet translated into targeted therapies.
What remains missing are randomised trials comparing surgery with modern medical management in asymptomatic patients, long-term data on fracture and cardiovascular outcomes for any drug, and validated biomarkers to stratify patients who will benefit from medical versus surgical treatment. No drug has been approved specifically for primary hyperparathyroidism on the basis of patient-important outcomes, and no genetic or molecular target has been turned into a therapy for sporadic disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Surgery · 2002 · 134 citations
Surgical Treatment of Hyperparathyroidism Improves Health-Related Quality of Life
AbstractHYPOTHESIS: The surgical treatment of primary hyperparathyroidism results in an improved health-related quality of life. DESIGN: Prospective cohort analysis of consecutive patients with primary hyperparathyroidism analyzed preoperatively and 1 year postoperatively. SETTING: Academic multispecialty referral clinic. PATIENTS: We prospectively evaluated 74 consecutive patients who underwent parathyroid exploration for primary hyperparathyroidism during a 15-month period. INTERVENTIONS: The Medical Outcomes Study Short-Form Health Survey (SF-36) was administered before consultation with a surgeon. Patients were categorized based on reason for referral as either asymptomatic (group 1; n = 43) or symptomatic (group 2; n = 29). All patients underwent parathyroid exploration and normalization of calcium levels postoperatively. The SF-36 was then re-administered after 1 year. MAIN OUTCOME MEASURES: Statistical analysis of preoperative and postoperative SF-36 scores, and comparisons with national norms. RESULTS: The SF-36 was completed preoperatively and 1 year postoperatively by 72 (97%) of 74 patients. When the results were compared with published national norms, the preoperative population was significantly impaired in 5 of 8 domains, whereas the postoperative one had improved and was nearly indistinguishable from the norm. In 7 of 8 domains, the postoperative scores were significantly improved compared with preoperative scores. Group 1 patients showed significant preoperative impairment in 3 domains and significantly improved in 2, whereas group 2 patients showed significant impairment and improvement in 7 domains. CONCLUSION: The surgical treatment of primary hyperparathyroidism is associated with durable, statistically significant improvements in health-related quality of life.
High-dose alfacalcidol improves anaemia in patients on haemodialysis
AbstractBACKGROUND: Alfacalcidol is efficient for treating secondary hyperparathyroidism in patients on maintenance haemodialysis (HD). Little is known about the direct impact of high-dose alfacalcidol on anaemia in end-stage renal failure. We therefore carried out a prospective study over 18 months to examine the direct effect of high-dose alfacalcidol on erythropoiesis in erythropoietin (rHuEpo)-dependent anaemic patients on HD for more than 6 months with moderate hyperparathyroidism. STUDY DESIGN: Twelve patients received oral alfacalcidol at a dosage of 6-7 micrograms per week and calcium carbonate during the first 12 months, calcium carbonate without alfacalcidol during the next 3 months, and again alfacalcidol and calcium carbonate during the last 3 months. Criteria for selection were haemoglobin < 10 g/dl, iPTH > 250 pg/ml, transferrin saturation (TS) > 25%, S-ferritin > 300 micrograms/l, and S-aluminium < 40 micrograms/l. RESULTS: Haemoglobin (Hb) and reticulocyte counts increased during the first phase, decreased and returned to a baseline prior to starting vitamin D treatment in the second phase, and again increased when alfacalcidol was reintroduced, whereas iPTH decreased during the first 3 months of the first phase and then remained stable, as did S-calcium, which increased during the first 3 months and then remained constant. S-phosphate increased during the first and third phases, and decreased during the second phase. Two patients during the first phase and one patient during the third phase presented hypercalcaemia; requiring a temporary discontinuation of alfacalcidol. CONCLUSION: High-dose alfacalcidol is efficient in anaemic patients with moderate hyperparathyroidism on maintenance HD and has a direct effect on erythropoietic cells regardless of serum calcium and iPTH levels.
Frontiers in Endocrinology · 2017 · 45 citations · open access
Contemporary Medical Management of Primary Hyperparathyroidism: A Systematic Review
AbstractIntroduction: Primary hyperparathyroidism is increasingly an asymptomatic disease at diagnosis, but the recognized guidelines for management are based on evidence obtained from studies on patients with symptomatic disease, and surgery is not always indicated. Other patients are unable to undergo surgery, and thus a medical treatment is warranted. This systematic review provides an overview of the existing literature on contemporary pharmaceutical options available for the medical management of primary hyperparathyroidism. Methods: Databases of medical literature were searched for articles including terms for primary hyperparathyroidism and each of the included drugs. Data on s-calcium, PTH, bone turnover markers, bone mass density and hard endpoints were extracted and tabulated, and level of evidence was determined. Changes in s-calcium were estimated and a meta-regression analysis was performed. Results: 1999 articles were screened for eligibility and 54 were included in the review. Weighted mean changes calculated for each drug in s-total calcium (mean change from baseline ± SEM) were: Pamidronate:(0.31 ± 0.034 mmol/l); Alendronate: (0.07 ± 0.05 mmol/l); Clodronate: (0.20±0.040 mmol/l); Mixed bisphosphonates: (0.16 ± 0.049 mmol/l); and Cinacalcet: (0.37 ± 0.013 mmol/l). The meta-analysis revealed a significant decrease of effect on s-calcium with time for the bisphosphonates (Coef. -0.049±0.023, p=0.035), while cinacalcet proved to maintain its effect on s-calcium over time. Bisphosphonates improved BMD while cinacalcet had no effect. Discussion: The included studies demonstrate advantages and drawbacks of the available pharmaceutical options that can prove helpful in the clinical setting. The great variation in how primary hyperparathyroidism is manifested requires that management should rely on an individual evaluation when counseling patients. Combining resorptive agents with calcimimetics could prove rewarding, but more studies are warranted.
AbstractPrimary hyperparathyroidism, a genetically heterogeneous disease, usually occurs as a sporadic disorder due to the presence of parathyroid adenoma/s, hyperplasia or, rarely, carcinoma. In the last decades familial forms of primary hyperparathyroidism have been described. Recognizing such forms is essential for a correct clinical management of affected individual subjects and families. In fact, primary hyperparathyroidism may be the typical feature of familial syndrome or alternatively only an associated disorder within the context of a more complex syndromic picture. Several responsible genes have been so far identified, making their mutational analysis possible, which provides not only early identification of asymptomatic gene carriers, but could also add new important knowledge of the molecular mechanisms underlying parathyroid tumorigenesis. Such mechanisms could, in the near future, become an ideal target for new therapeutic strategies of primary hyperparathyroidism.
Annales d Endocrinologie · 2025 · 6 citations · open access
Chapter 9: Indications for the treatment of primary hyperparathyroidism
AbstractThe choice of therapeutic method for the management of primary hyperparathyroidism depends on the severity of the disease and its complications at the time of diagnosis, the specific situation of each patient and his/her natural history, and assessment of the risk/benefit ratio for each method (surgery, local destruction or drugs). This chapter summarizes the indications for the treatment of primary hyperparathyroidism, based on the international literature available as of December 31st, 2023.
Parathyroid carcinoma presenting with pathologic fracture: Case report and review of the literature
AbstractBACKGROUND: Parathyroid carcinoma is a rare neoplasm representing <1% of primary hyperparathyroidism cases. It is often not diagnosed until surgical exploration as a preoperative diagnosis is often not possible. Thus, preoperative staging for most patients is not feasible and this may compromise the treatment strategy. METHODS AND RESULTS: We report a case of a 29-year-old man presenting with avulsion fracture of the right elbow after a trivial fall. Neck exploration revealed an enlarged left lobe focally adherent to the larynx and trachea. Final pathology revealed parathyroid carcinoma with focally positive margin at the site of tracheal invasion. CONCLUSION: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. The etiology of parathyroid carcinoma is usually obscured, and the initial operation offers the best chance for cure.
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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