DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for episodic pain syndrome, familial, 2 — 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 moduleEpisodic pain syndrome, familial, 2 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 episodic pain syndrome, familial, 2 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 10 (SCN10A) — SCN10A 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 4-chlorophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7WE4 · 2.7 Å · ligand 5-(4-chlorophenyl)-~{N}-(3,5-dimethoxyphenyl)furan-2-carboxamide (95T). Experimental structure, not a prediction.
What the evidence adds up to
A gain-of-function mutation in TRPA1 (N855S) causes an autosomal-dominant familial episodic pain syndrome characterised by episodes of debilitating upper body pain triggered by fasting and physical stress. The mutant channel showed a 5-fold increase in inward current on activation at normal resting potentials. TRPA1 antagonists inhibit the mutant channel in vitro. A 2022 case report and literature review describes a 3-year-old boy with pain in both forearms and lower limbs below the knees for more than 3 years, with no abnormalities in blood tests, imaging, or inflammatory markers; genetic testing identified two heterozygous mutations in SCN11A (c.674G>T and c.671T>C). Only 21 cases of FEPS3 caused by SCN11A mutation had been reported at that time. A 2020 description notes that episodes last 60–90 minutes, respond poorly to conventional analgesia, and are accompanied by dyspnoea, tachycardia, sweating, pallor, peribuccal cyanosis, and abdominal wall stiffness.
A 2008 study of Dutch patients with complex regional pain syndrome found 31 families with two or more affected relatives, but no clear inheritance pattern. Familial CRPS patients had a younger age at onset and more often had multiple affected extremities and dystonia compared with sporadic cases. A 2012 twin family study of growing pains reported casewise concordance of 0.85 for monozygotic pairs and 0.36 for dizygotic pairs (p < 0.001), and found that 23% of twin individuals with growing pains met restless legs syndrome criteria compared with 8% of those without (p = 0.03). A 2023 case report describes a 12-year-old with familial dysautonomia (Riley-Day syndrome) who, contradictorily, developed increased pain perception and allodynia after repetitive orthopaedic procedures.
What is still missing is a randomised controlled trial of any TRPA1 antagonist in patients with the confirmed TRPA1 mutation, and systematic genotyping of larger episodic pain cohorts to establish the prevalence of TRPA1 versus SCN11A mutations. The natural history and optimal trigger-avoidance strategies remain unquantified, and no trial has tested whether early intervention alters the long-term course. Patient stratification by genotype and trigger profile is needed before any targeted therapy can be evaluated.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuron · 2010 · 444 citations · open access
A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome
AbstractHuman monogenic pain syndromes have provided important insights into the molecular mechanisms that underlie normal and pathological pain states. We describe an autosomal-dominant familial episodic pain syndrome characterized by episodes of debilitating upper body pain, triggered by fasting and physical stress. Linkage and haplotype analysis mapped this phenotype to a 25 cM region on chromosome 8q12-8q13. Candidate gene sequencing identified a point mutation (N855S) in the S4 transmembrane segment of TRPA1, a key sensor for environmental irritants. The mutant channel showed a normal pharmacological profile but altered biophysical properties, with a 5-fold increase in inward current on activation at normal resting potentials. Quantitative sensory testing demonstrated normal baseline sensory thresholds but an enhanced secondary hyperalgesia to punctate stimuli on treatment with mustard oil. TRPA1 antagonists inhibit the mutant channel, promising a useful therapy for this disorder. Our findings provide evidence that variation in the TRPA1 gene can alter pain perception in humans.
Familial occurrence of complex regional pain syndrome
AbstractGenetic factors are suggested to play a role in complex regional pain syndrome (CRPS), but familial occurrence has not been extensively studied. In the present study we evaluated familial occurrence in Dutch patients with CRPS. Families were recruited through the Dutch Association of CRPS patients and through referral by clinicians. The number of affected members per family, the phenotypic expression and inheritance were assessed. Demographic and clinical characteristics of familial CRPS (fCRPS) patients were compared with those of sporadic CRPS (sCRPS) patients from a Dutch population-based study and with a group of sCRPS patients that was proportionally matched for referral center of the fCRPS probandi to control for referral bias. Thirty-one CRPS families with two or more affected relatives were identified, including two families with five, four with four, eight with three and 17 with two affected relatives. In comparison with sCRPS patients, fCRPS patients had a younger age at onset and more often had multiple affected extremities and dystonia. We conclude that CRPS may occur in a familial form, but did not find a clear inheritance pattern. Patients with fCRPS develop the disease at a younger age and have a more severe phenotype than sporadic cases, suggesting a genetic predisposition to develop CRPS.
Growing pains: Twin family study evidence for genetic susceptibility and a genetic relationship with restless legs syndrome
AbstractBACKGROUND: Growing pains (GP) is a prevalent familial childhood disorder of unknown aetiology. Familial occurrence of GP, and individual and familial association of GP with restless legs syndrome (RLS) has been reported. METHODS: We applied a twin family design to search for evidence of genetic susceptibility to GP, and for a genetic relationship between GP and RLS. The parents of 1843 twin pairs aged 3-16 years were administered a questionnaire, which identified 88 pairs with at least one twin individual fulfilling criteria for GP. Standard questionnaires for history of GP and RLS were completed for these twin pairs, their siblings and parents. RESULTS: Twenty-five of 34 monozygotic (MZ) pairs were concordant for GP, compared with 12 of the 54 dizygotic (DZ) pairs. The casewise concordance was 0.85 and 0.36 for MZ and DZ pairs, respectively (p < 0.001). The lifetime GP prevalence for relatives of twins with GP was 51% for non-twin siblings, 47% for parents. Twenty-three percent of twin individuals with GP met RLS criteria compared with 8% of twin individuals without GP (p = 0.03). Of the twins with GP concordance, 19% met RLS criteria compared with 2% of twins with GP discordance (p = 0.01). In two MZ pairs, one had GP and the other RLS. The lifetime prevalence of RLS was 40% for mothers, and 24% for fathers and 18% for non-twin siblings. CONCLUSION: This first twin family study of GP provides evidence for a genetic aetiology and for a genetic relationship to RLS.
Annals of Translational Medicine · 2022 · 3 citations · open access
Familial episodic pain syndrome: a case report and literature review
AbstractAbstract: The purpose of this case report and literature review is to show that familial episodic pain syndrome (FEPS) is a non-inflammatory genetically inherited pain syndrome. A 3-year-old boy presented at our hospital with pain in both his forearms and lower limbs below the knees for more than 3 years. There were no abnormalities in the blood tests, blood smears, liver and kidney function tests, trace elements tests, cellular immunity test, humoral immunity test, autoantibody tests, C-reactive protein (CRP) test, erythrocyte sedimentation rate (ESR) test, and tumor-related and bone marrow cytology examinations. Additionally, the imaging examination results showed no abnormalities. From the patient’s medical history, we found that the mother of the child had a family history of a similar disease. To date, only 21 cases of FEPS3 caused by the sodium voltage-gated channel alpha subunit 11A (SCN11A) gene mutation have been reported. Although the age of onset is different, most of them are inherited in families. The results of the genetic examination revealed that the pain mainly came from the genetic inheritance of the maternal family line. The whole exon gene test revealed that the pain was caused by 2 heterozygous mutations of c.674G > T and c.671T > C in the SCN11A gene.
Revista de Medicina da UFC · 2023 · 1 citations · open access
A rare case of postoperative pain in congenital analgesia: case report
AbstractObjective: we describe a case of a patient with familial dysautonomia and postoperative pain. Methodology: clinical follow-up for 10 years in a tertiary pediatric hospital. Results: it is a 12 years old teenager, diagnosed with Riley-Day Syndrome, after undergoing various orthopedic surgical procedures, evolves with changes in pain perception, in systematic assessments. Conclusion: Family Disautonomy is one of the most common Hereditary Sensory and Autonomic Neuropathies (HSAN). Children gradually evolve with sensory changes, leading to a progressive decrease in pain perception. In addition, spinal deformities and recurrent orthopedic trauma can occur. The reported patient presents, contradictorily, an increase in the perception of pain and allodynia after undergoing repetitive orthopedic procedures.
Familial episodic pain syndrome with predominantly upper body involvement
AbstractOpe n Pe e r Re v ie w on Qe ios Ope n Pe e r Re v ie w on Qe ios Familial episodic pain syndrome with predominantly upper body involvement INSERM Source INSERM.(1999).Orphanet: an online rare disease and orphan drug data base.Familial episodic pain syndrome with predominantly upper body involvement.ORPHA:391389 Familial episodic pain syndrome with predominantly upper body involvement is a subtype of familial episodic pain syndrome characterized by episodes of severe debilitating pain mainly affecting shoulders, thorax and arms (occasionally radiating to the abdomen and legs), triggered by fasting, fatigue, cold temperatures or physical exercise, which last for 60-90 min and respond poorly to conventional analgesia.Intense pain episodes are accompanied by dyspnea, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall and are followed by a period of exhaustion and somnolence.
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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