DeCure for Progressive familial heart block, type 1A
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for progressive familial heart block, type 1A — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleProgressive familial heart block, type 1A maps to a 2-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
approvedMoricizineApproved drug
Structures already discussed alongside progressive familial heart block, type 1a in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
transient receptor potential cation channel subfamily M member 4 (TRPM4) — TRPM4 is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has [(2r)-1-octadecanoyloxy-3-[oxidanyl-[(1r,2r,3s,4r,5r,6s)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho
ryl]oxy-propan-2-yl] (8z)-icosa-5,8,11,14-tetraenoate bound in it, shown as sticks.
Loading structure…
helix sheet 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9MRT · 2.44 Å · ligand [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho
ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate (PT5). Experimental structure, not a prediction.
What the evidence adds up to
A 1975 study described a family in which complete heart block developed late in life, apparently inherited as an autosomal dominant trait. Two octogenarian brothers had symptomatic complete heart block, and their younger relatives had asymptomatic conduction abnormalities. Neurological disease was present in one proband, but investigations suggested this was a fortuitous association. No sample size or survival data were given.
A 1977 report described a family with two siblings who had congenital complete heart block with resultant congestive heart failure, a father and paternal grandfather with adult-onset conduction defects, and a mother with systemic lupus erythematosus. The authors reviewed the literature on familial complete heart block and suggested that so-called pure congenital-onset familial heart block, originally thought to be genetic, might have an important environmental component related to ongoing maternal factors such as systemic lupus erythematosus.
A 2007 review noted that complete heart block, either congenital or acquired, in children and patients with congenital heart disease is a relatively frequent occurrence requiring therapy. The review stated that the natural history of this condition has been distorted by the advent of new diagnostic and therapeutic modalities, and that traditional treatment strategies using right ventricular apical pacing may have inadvertent deleterious effects on cardiac function. No survival or response rates were reported.
What is still missing is any prospective trial data for progressive familial heart block type 1A specifically, any genetic confirmation of the diagnosis in the reported families, and any stratification of patients by genotype or maternal antibody status. No drug therapy was tested or mentioned in any of these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Circulation · 1977 · 68 citations · open access
Familial congenital complete heart block and maternal systemic lupus erythematosis.
AbstractA family is reported in which two siblings had congenital complete heart block with resultant congestive heart failure, the father and paternal grandfather show adult-onset conduction defects, and the mother has systemic lupus erythematosis. The interaction of heredity and environment is discussed in this context. A review of the literature on familial complete heart block suggests that so-called pure congenital-onset familial heart block, originally felt to be genetic, may in fact have an important enivronmental component, specifically related to ongoing maternal factors such as systemic lupus erythematosis.
Natural History and Current Therapy for Complete Heart Block in Children and Patients with Congenital Heart Disease
AbstractComplete heart block, either congenital or acquired, in children and patients with congenital heart disease is a relatively frequent occurrence requiring therapy. The natural history of this condition has been distorted by the advent of new diagnostic and therapeutic modalities. The therapy of complete heart block is evolving with new data suggesting that traditional treatment strategies utilizing right ventricular apical pacing may have inadvertent deleterious effects on cardiac function. In the following manuscript, the natural history of complete heart block is reviewed and the current therapy examined.
FAMILIAL LATE ONSET HEART BLOCK: A CLINICO-PATHOLOGICAL STUDY
AbstractA family is reported in which complete heart block developed late in life, apparently inherited as an autosomal dominant trait. Two octogenarian brothers had symptomatic complete heart block, and their younger relations asymptomatic conduction abnormalities. Neurological disease was present in one proband; investigations suggested that this was a fortuitous association.
Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · 1992 · 0 citations
Exacerbation of Congestive Heart Failure Secondary to Moricizine
AbstractMoricizine, a recently approved phenothiazine antiarrhythmic agent, is reported to be associated with a low frequency of congestive heart failure. A 61-year-old man with a history of congestive heart failure and ischemic heart disease began taking moricizine 250 mg every 8 hours to suppress his monomorphic sustained ventricular tachycardia. After five doses he became progressively short of breath and was in pulmonary edema. Moricizine was discontinued, intravenous diuretics were administered, and the patient's clinical status stabilized. Twelve hours later, however, he developed polymorphic ventricular tachycardia and was not successfully resuscitated. Despite claims as to its safety, limited data strongly suggest that moricizine, like other antiarrhythmics, may be detrimental in patients with preexisting ventricular dysfunction, and should be prescribed with caution.
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.
