DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for juvenile Paget disease — 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 moduleJuvenile Paget disease 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 juvenile paget disease 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
TNF receptor superfamily member 11b (TNFRSF11B) — TNFRSF11B 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3URF · 2.701 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The three abstracts concern different conditions that share the name Paget but are not the same disease. The first describes three women with extramammary Paget disease, a skin cancer, treated with a topical 1:1 mixture of fluorouracil 5% cream and calcipotriene 0.005% cream. All three had recurrent disease after surgery or irradiation and had become refractory to imiquimod. After starting the combination, all showed clinical improvement in symptoms and lesion appearance, and two of the three had histopathological signs of decreased tumour burden. The treatment was well tolerated. Application frequency varied from one to two days per month to four consecutive days every two weeks. This is a retrospective case series of three patients, not a controlled trial, and the authors describe it as palliative.
The second abstract examines genetic polymorphisms in 69 patients with Paget's disease of bone and 120 healthy controls. It found that the XbaI and PvuII genotype distributions of the oestrogen receptor-alpha gene were significantly different between patients and controls, and the calcium-sensing receptor A986S genotype frequency also differed significantly. No significant effect of these polymorphisms on bone mineral density or biochemical markers of bone turnover was observed. The authors conclude these polymorphisms may contribute to genetic susceptibility but call for further studies.
The third abstract, from 1977, states that Paget's disease of bone affects about 3% of the population over age forty, may be genetically transmitted, and notes a possible viral aetiology. It lists then-available treatments: calcitonin loses effectiveness in many patients over months, mithramycin has significant toxicity, and diphosphonates tend to cause osteomalacia.
No abstract addresses juvenile Paget disease specifically. The topical combination of fluorouracil and calcipotriene was tested only in extramammary Paget disease, not in bone disease. The genetic and treatment abstracts concern adult Paget's disease of bone. What is missing for juvenile Paget disease is any dedicated clinical trial, any pharmacokinetic or safety data in children, and any evidence that either topical or systemic agents discussed here would alter the bone remodelling defect that defines the juvenile form.
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 Plastic Surgery · 1984 · 30 citations
Surgical Treatment of Genital Paget’s Disease in Men
AbstractTwenty-one men with genital Paget's disease were treated in our clinic from 1968 to 1983. We report our policy regarding treatment of the clinical disorder, particularly our surgical approach. We also stress that, when considering treatment, the circumstances of the aged patients should take precedence over aggressive treatment of the clinical state of the dermal disease.
Topical Combination of Fluorouracil and Calcipotriene as a Palliative Therapy for Refractory Extramammary Paget Disease
AbstractIMPORTANCE: Extramammary Paget disease (EMPD), a rare intraepithelial adenocarcinoma, poses a therapeutic challenge with high postoperative recurrence rates and a limited number of effective local treatment options. OBJECTIVE: To describe the use and efficacy of a topical combination of fluorouracil and calcipotriene as a palliative therapy for refractory EMPD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series of 3 women with recurrent, refractory EMPD was conducted at Beth Israel Deaconess Medical Center, Boston, Massachusetts and Washington University School of Medicine, St Louis, Missouri. All patients were treated with a 1:1 mixture of fluorouracil, 5%, cream and calcipotriene, 0.005%, cream or ointment. MAIN OUTCOMES AND MEASURES: Clinical and histopathological findings. RESULTS: All 3 women (1 in her 50s, 2 in their 70s) presented with recurrent EMPD (vulvar, perianal, and perioral) after surgery and/or irradiation, and their EMPD was refractory to treatment with imiquimod, 5%, cream. Owing to disease progression and/or intolerable adverse effects from imiquimod, the patients began treatment with a 1:1 mixture of fluorouracil, 5%, cream and calcipotriene, 0.005%, cream. This treatment, which was well tolerated, was followed by clinical improvement in symptoms and appearance of the lesions in all 3 cases and histopathological signs of decreased tumor burden in 2 cases. Patients applied the combination topical therapy to affected areas with differing frequencies, ranging from 1 to 2 days per month to 4 consecutive days every 2 weeks. CONCLUSIONS AND RELEVANCE: Extramammary Paget disease frequently recurs even after aggressive surgical management and can be refractory to many topical and locoregional therapies. Palliative treatment with a combination of fluorouracil and calcipotriene may be a viable option for patients with recurrent, refractory EMPD.
Vitamin D receptor, oestrogen receptor- and calcium-sensing receptor genotypes, bone mineral density and biochemical markers in Paget's disease of bone
AbstractOBJECTIVES: The significance of genetic polymorphisms in the development of Paget's disease of bone is unclear at present. METHODS: We analysed the BsmI polymorphism of the vitamin D receptor (VDR) gene, the PvuII and XbaI polymorphisms of the oestrogen receptor-alpha (ER alpha) gene, and the A986S polymorphism of the calcium-sensing receptor (CaSR) gene in 69 pagetic patients and 120 healthy subjects. We also examined the relationship of these polymorphisms with lumbar spine and femoral neck BMD as well as with biochemical parameters (serum alkaline phosphatase, osteocalcin and parathyroid hormone) in Paget's disease. RESULTS: The XbaI and PvuII genotype distributions of the ER alpha gene were significantly different between patients with Paget's disease and control subjects (P<0.001). Also, the CaSR A986S genotype frequency was significantly different between pagetic patients and controls (P<0.01). No significant effect of gene polymorphisms on BMD or biochemical parameters of bone turnover was observed. CONCLUSION: Our results suggest that the ER alpha PvuII/XbaI and CaSR A986S polymorphisms may contribute to genetic susceptibility to Paget's disease. However, further studies are required to investigate the underlying pathomechanism and to replicate the associations.
AbstractPaget's disease affects approximately 3% of the population over age forty. It may be genetically transmitted (autosomal-dominant), but recent evidence suggests a viral etiology. Effective agents for control of the disorder have been developed over the past decade, but all have significant drawbacks. Calcitonin tends to lose its effectiveness in significant numbers of patients over a few months, mithramycin has significant toxicity, and diphosphonates tend to cause osteomalacia.
AbstractPaget's disease is a metabolic bone disease characterized by abnormalities of bone turnover, structure and architecture. The disease is of unknown aetiology, although both genetic and environmental factors have been implicated. Treatment is indicated for patients with active disease and currently bisphosphonates are the first-choice management option.
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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