DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for long QT syndrome 3 — 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 moduleLong QT syndrome 3 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 long qt syndrome 3 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 5 (SCN5A) — SCN5A 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 qdndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6LQA · 3.3 Å · ligand Quinidine (QDN). Experimental structure, not a prediction.
What the evidence adds up to
The 1983 paper calls for a prospective registry of idiopathic long QT syndrome patients, noting that pathogenetic mechanisms were largely but not completely understood at that time. No treatment data or patient numbers are given in that abstract.
A 2006 review of drug-induced long QT syndrome states that most QT-prolonging drugs block a specific potassium channel, though novel mechanisms altering protein trafficking have been discovered. The progression to torsade de pointes may be less related to the degree of QT prolongation than to drug effects on transmural dispersion or variability of repolarisation. The review notes that the degree of QT prolongation is an imperfect predictor of risk for torsade de pointes. No specific drugs, survival rates, or response rates are reported.
A separate 2006 review of congenital long QT syndrome reports that genetic testing, now commercially available, will determine the defect in as many as 75% of subjects in a family with suspected disease. The mainstay of therapy continues to be beta-blockers, and implantable cardioverter-defibrillators are indicated in patients at high risk for malignant arrhythmias. The review states that long QT syndrome is one of the leading causes of sudden cardiac death. No sample sizes or survival numbers are given.
A 2001 study of a single large French family with long QT1 syndrome followed over 25 years found that in adult male mutation carriers the QTc interval normalised after puberty, but not in females. Dynamic analysis of the QT interval from Holter recordings permitted individual diagnosis in mutation carriers even when the QTc interval was normal. The abstract reports that up to 70% of gene carriers may have a normal QTc interval. No treatment outcomes or survival data are reported. The 2010 Japanese abstract describes a follow-up survey of QT-prolonging medicines and development of screening software for drug-induced QT prolongation; no results, patient numbers, or outcomes are provided.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Cardiology · 2006 · 228 citations
Drug-induced long QT and torsade de pointes: recent advances
AbstractPURPOSE OF REVIEW: A wide array of drugs can cause marked QT prolongation with the associated risk of torsade de pointes. The large number of drugs with this potential, the correspondingly large number of patients exposed to such drugs, and the potentially fatal outcome make drug-induced long QT syndrome an important public health problem. This review focuses on mechanisms underlying QT prolongation and proarrhythmia, risk factors, including the role of genetic variants, and the unifying framework of reduced repolarization reserve. RECENT FINDINGS: While most drugs that prolong the QT block a specific potassium channel, novel mechanisms altering protein trafficking have been discovered. The progression to torsade de pointes may be less related to degree of QT prolongation than to drug effects on transmural dispersion or variability of repolarization. Our understanding of certain predisposing risk factors has been further refined. SUMMARY: Ongoing research continues to elucidate the mechanisms underlying drug-induced long QT syndrome. Importantly, studies are establishing improved predictors of risk for progression to torsade de pointes, in addition to the degree of QT prolongation, which is an imperfect predictor. Nonetheless, drug-induced long QT syndrome and torsade de pointes pose unique challenges for clinicians, researchers, drug-development programs, and regulatory agencies.
The idiopathic long QT syndrome: the need for a prospective registry
AbstractThe pathogenetic mechanisms of idiopathic long QT syndrome have been largely, although not completely, understood; however, several critical issues highly relevant to the clinical management of patients affected by the syndrome need to be clarified. For this purpose, physicians are invited to a registry of such patients.
Current Opinion in Pediatrics · 2006 · 38 citations
Advances in congenital long QT syndrome
AbstractPURPOSE OF REVIEW: Dramatic advances have been made in understanding of both the genetics and the phenotypic expression of congenital long QT syndrome. This paper reviews recent clinically relevant literature. RECENT FINDINGS: Long QT syndrome is one of the leading causes of sudden cardiac death. This syndrome, once diagnosed by a clinical profile, has been more clearly defined by specific gene defects causing ion channel abnormalities in the beating heart. Genetic testing for long QT syndrome, once available only through research laboratories, is now commercially available. Diagnosis, risk assessment, and management are increasingly being guided by gene-specific diagnoses. In a family with suspected disease, the genetic test will determine the defect in as many as 75% of subjects. Once the diagnosis is made, the mainstay of therapy continues to be beta-blockers. Implantable cardioverter-defibrillators are indicated in patients at high risk for malignant arrhythmias. SUMMARY: Long QT syndrome is one of the first cardiovascular diseases to see the dramatic changes that bench research can bring to the clinical arena. Future research is needed to determine the gene defect in the remaining 25% of patients with suspected long QT syndrome and in risk stratification.
European Heart Journal · 2001 · 28 citations · open access
Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype
AbstractAIMS: In families with the long QT syndrome penetrance may be low: up to 70% of gene carriers may have a normal QTc interval. These patients require therapy, similar to that in those with longer QTc intervals, but identifying them, using molecular analysis, is difficult to apply on a large scale. A large French family affected by the long QT1 syndrome was followed-up over a 25-year period. In adult males but not in females, the QTc interval normalized after puberty. We aimed to find clinical criteria, based on ambulatory ECG recordings so that we could improve diagnosis in affected members with a normal QTc. METHODS AND RESULTS: Linkage analysis and direct sequencing were an indicator of the long QT1 gene in our family. Reverse transcription-polymerase chain reaction analysis demonstrated abnormal transcripts in lymphocytes from silent gene carriers. The functional profile of mutated protein isoforms was investigated using the patch-clamp technique. Dynamic analysis of ventricular depolarization was conducted using Holter recordings in patients, and in sex- and age-matched controls. Circadian variations of the QTc interval and the QT/RR relationship were assessed. Sensitivity, specificity, and predictive values were evaluated for proposed clinical criteria. We found that dynamic analysis of the QT interval permitted individual diagnosis in mutation carriers even when the QTc interval was normal (adult males). CONCLUSION: Dynamic analysis of the QT interval is of diagnostic value in the long QT1 syndrome in patients with a normal phenotype. Clinical implications include improvement in screening and patient management.
Sapporo Medical University Institutional Repository · 2010 · 0 citations · open access
QT延長症候群原因医薬品の追跡調査とスクリーニングソフトウェアの作成
AbstractIn recent years, the mechanisms that cause congenital and secondary long QT syndrome have been elucidated in considerable detail. We have attempted to determine of treatment courses for individual patients when it is necessary to administer medicines associated with QT prolongation. Therefore we decided to conduct a follow-up survey of these medicines, and aim to develop a software for avoidance and early recognition of drug-induced QT prolongation in association with cardiovascular internal medicine at our hospital.
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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