DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for erythromelalgia — 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 moduleErythromelalgia 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 erythromelalgia 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
sodium voltage-gated channel alpha subunit 9 (SCN9A) — SCN9A 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…
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RCSB Protein Data Bank · entry 7W9K · 2.2 Å · ligand O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (P5S). Experimental structure, not a prediction.
What the evidence adds up to
A retrospective review of 168 patients seen at the Mayo Clinic between 1970 and 1994 found that erythromelalgia carries significantly increased mortality compared with the US general population of the same age and sex (P<.001). After a mean follow-up of 8.7 years, only 10.6% of patients reported complete resolution of symptoms; 31.9% reported worsening, 26.6% no change, and 30.9% improvement. On a standard health status questionnaire, scores were significantly diminished in all but one health domain. The cohort was 72.6% female, mean age at presentation 55.8 years (range 5–91), and 97.0% had intermittent rather than constant symptoms. Symptoms predominantly involved the feet (88.1%) and hands (25.6%). Six patients (3.6%) had a first-degree relative with the condition.
A 2019 review distinguishes primary erythromelalgia, now defined by specific genetic mutations, from secondary erythromelalgia, which is often associated with underlying medical disorders. A 2006 case report and literature review notes that the diagnosis depends on a thorough history and physical exam during a painful episode, plus testing to exclude other causes. The same report states that despite multiple treatment options, erythromelalgia is a challenging disease to manage effectively, and that early recognition and treatment may offer the best probability of remission or significant improvement.
No controlled trial data are reported in these abstracts. The natural history study is retrospective and from a single tertiary centre, limiting generalisability. What is missing is prospective, longitudinal data with standardised outcome measures, a clear stratification of primary versus secondary cases, and any randomised trial of a specific drug. The genetic basis of primary erythromelalgia is now known, but no therapy targeting that mechanism has been tested in a controlled fashion.
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 Dermatology · 2000 · 251 citations
Natural History of Erythromelalgia
AbstractOBJECTIVE: To describe the demographics, presentation, and outcome in patients with erythromelalgia--a rare and poorly understood clinical syndrome defined by the triad of red, hot, painful extremities. DESIGN: Retrospective medical record review with follow-up by survey questionnaire. SETTING: Large tertiary care medical center. SUBJECTS: Patients with erythromelalgia examined at the Mayo Clinic, Rochester, Minn, between 1970 and 1994. INTERVENTION: The medical records of 168 patients were analyzed. Follow-up data, which consisted of answers to 2 survey questionnaires or the most recent information in the medical record from patients still alive and death certificates or reports of death for those deceased patients, were obtained for all but 13 patients. MAIN OUTCOME MEASURES: Survival, morbidity, and quality of life. RESULTS: All patients were white; 122 (72.6%) were female, and 46 (27.4%) were male. At presentation, the patients' mean age was 55.8 years (age range, 5-91 years). Symptoms had been present since childhood in 7 patients (4.2%). Six patients (3.6%) had a first-degree relative with erythromelalgia. Symptoms were intermittent in 163 patients (97.0%) and constant in 5 (3.0%). Symptoms predominantly involved feet (148 patients [88.1%]) and hands (43 patients [25.6%]). Kaplan-Meier survival curves revealed a significant decrease in survival compared with that expected in persons of similar age and of the same sex (P<.001). After a mean follow-up of 8.7 years (range, 1.3-20 years), 30 patients (31.9%) reported worsening of, 25 (26.6%) no change in, 29 (30.9%) improvement in, and 10 (10.6%) complete resolution of the symptoms. On a standard health status questionnaire, scores for all but one of the health domains were significantly diminished in comparison with those in the US general population. CONCLUSION: Erythromelalgia is a syndrome with significantly increased mortality and morbidity compared with the US general population.
Clinical and Experimental Dermatology · 2019 · 92 citations · open access
Review of primary and secondary erythromelalgia
AbstractErythromelalgia is a condition characterized by episodic pain, erythema and temperature of the extremities, which is relieved by cooling and aggravated by warming. It is useful to review this topic in light of recent discoveries of the genetic mutations that now define primary erythromelalgia, as opposed to secondary erythromelalgia, which is often associated with underlying medical disorders.
Erythromelalgia: A Case Report and Literature Review
AbstractOBJECTIVE: Erythromelalgia is a rare condition, of uncertain etiology, characterized by episodic erythema, intense burning pain and warmth of the hands and/or feet, and when chronic, associated with significant disability. The diagnosis is based on a thorough history and physical exam during a painful episode along with diagnostic testing to exclude other causes. This paper describes the unique syndrome of erythromelalgia through a case report and literature review. DESIGN: Case presentation and literature review. PATIENTS: A 44-year-old male with erythromelalgia. CONCLUSIONS: Despite multiple treatment options, erythromelalgia is a challenging disease to effectively manage. Early recognition and treatment may offer patients the best probability of achieving remission or significant improvement.
Successful Treatment of Erythromelalgia With Intrathecal Hydromorphone and Clonidine
AbstractOBJECTIVE: The objective of this study was to determine if intractable pain from erythromelalgia could be successfully treated with intrathecal hydromorphone and clonidine. DESIGN: A single case of pain from erythromelalgia refractory to multiple treatment modalities was examined and treated. SETTING: The setting is an outpatient pain clinic at a major university teaching hospital. PATIENT: Our patient is an 82-year-old woman with hypertension and peripheral vascular disease. INTERVENTION: Intrathecal opioid and an alpha2-agonist were administered. OUTCOME MEASURES: Outcome was determined by means of patient self-report during office follow-up visits. RESULTS AND CONCLUSIONS: Administration of intrathecal opioid and an alpha2-agonist can be effective in the treatment of the pain of erythromelalgia and offers an alternative pain treatment modality for patients with unremitting pain refractory to more conservative therapy.
Translational Perioperative and Pain Medicine · 2019 · 9 citations · open access
Case Report and Literature Review: Interventional Management of Erythromelalgia
AbstractErythromelalgia is a rare and very difficult to treat pain syndrome that usually presents as severe bilateral burning pain in the extremities. Here we present a case of a 34-year-old female with erythromelalgia who we treated successfully with a lumbar epidural infusion of ropivacaine and fentanyl. The patient had complete relief shortly after the epidural infusion, and she remained stable with only minor pain two weeks and nine months later. With this case, we have reviewed the interventional treatments of erythromelalgia. We suggest epidural infusion as the first line interventional management, followed by sympathetic block. Spinal cord stimulation can be considered if other interventional managements fail.
AbstractErythromelalgia is a rare disease characterized by intense erythema, burning pain and increased temperature in the distal of the extremities. Primary forms and secondary forms have been described, most commonly with essential thrombocythemia and policythemia vera. The authors describe a fifteen year old patient with primary erythromelalgia and discuss the pathogenic, clinical and therapeutic features of this disease.
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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