DeCure for Familial episodic pain syndrome with predominantly lower limb involvement
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial episodic pain syndrome with predominantly lower limb involvement — 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 moduleFamilial episodic pain syndrome with predominantly lower limb involvement 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 familial episodic pain syndrome with predominantly lower limb involvement 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.
What the evidence adds up to
Familial episodic pain syndrome (FEPS) is a non-inflammatory, genetically inherited condition with early-childhood onset of severe episodic pain mainly affecting the distal extremities, which tends to attenuate or diminish with age. A 2022 review describes four subtypes — FEPS1, FEPS2, FEPS3, and FEPS4 — caused by gain-of-function mutations in TRPA1, SCN10A, SCN11A, and SCN9A, respectively. A 2022 case report of a 3-year-old boy with pain in both forearms and lower limbs below the knees found no abnormalities in blood tests, blood smears, liver and kidney function, trace elements, cellular and humoral immunity, autoantibodies, C-reactive protein, erythrocyte sedimentation rate, tumour-related markers, bone marrow cytology, or imaging. Genetic examination revealed two heterozygous mutations in SCN11A: c.674G > T and c.671T > C. The report notes that only 21 cases of FEPS3 caused by SCN11A mutation had been documented at that time.
A 2024 Japanese nationwide study recruited 212 patients using provisional clinical diagnostic criteria and performed genetic testing for SCN11A, SCN10A, and SCN9A. Pathogenic or likely pathogenic variants were found in 64 patients (30.2%): 42 (19.8%) in SCN11A, 14 (6.60%) in SCN10A, and 8 (3.77%) in SCN9A. Among patients with these variants, the proportions meeting the tentative clinical criteria were 89.1% for SCN11A, 52.0% for SCN10A, and 54.5% for SCN9A, suggesting the criteria are most valid for SCN11A. The authors state that undiagnosed patients may be unexpectedly prevalent in Japan.
No controlled treatment trial data are reported in any of these abstracts. The 2022 review mentions that some FEPS patients show relative treatability and favourable prognosis, but gives no specific drug, response rate, or survival numbers. What is missing is a prospective trial with a defined drug intervention, a standardised outcome measure for pain episodes, and patient stratification by genotype — without which no treatment can be recommended.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Pain Research · 2022 · 8 citations · open access
Familial Episodic Pain Syndromes
AbstractAbstract: Over the past decades, advances in genetic sequencing have opened a new world of discovery of causative genes associated with numerous pain-related syndromes. Familial episodic pain syndromes (FEPS) are one of the distinctive syndromes characterized by early-childhood onset of severe episodic pain mainly affecting the distal extremities and tend to attenuate or diminish with age. According to the phenotypic and genetic properties, FEPS at least includes four subtypes of FEPS1, FEPS2, FEPS3, and FEPS4, which are caused by mutations in the TRPA1, SCN10A, SCN11A , and SCN9A genes, respectively. Functional studies have revealed that all missense mutations in these genes are closely associated with the gain-of-function of cation channels. Because some FEPS patients may show a relative treatability and favorable prognosis, it is worth paying attention to the diagnosis and management of FEPS as early as possible. In this review, we state the common clinical manifestations, pathogenic mechanisms, and potential therapies of the disease, and provide preliminary opinions about future research for FEPS. Keywords: familial episodic pain syndromes, voltage-gated sodium channel, transient receptor potential A1, dorsal root ganglia, nociceptive pain
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.
International Journal of Molecular Sciences · 2024 · 2 citations · open access
Genetic Analysis of SCN11A, SCN10A, and SCN9A in Familial Episodic Pain Syndrome (FEPS) in Japan and Proposal of Clinical Diagnostic Criteria
AbstractFamilial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A, SCN10A, and SCN9A, which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A, SCN10A, and SCN9A. In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A, SCN10A, and SCN9A, respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.
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.
