DeCure for Polyhydramnios, megalencephaly, and symptomatic epilepsy
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for polyhydramnios, megalencephaly, and symptomatic epilepsy — 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 modulePolyhydramnios, megalencephaly, and symptomatic epilepsy 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 polyhydramnios, megalencephaly, and symptomatic epilepsy 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
STE20 related adaptor alpha (STRADA) — STRADA 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8VSU · 2.86 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
A 2021 case report describes a female patient with the typical clinical features of polyhydramnios, megalencephaly and symptomatic epilepsy syndrome (PMSE), caused by a novel homozygous missense mutation in STRADA (c.792T>A, p.Ser264Arg) in exon 10. The syndrome was first defined in 16 Old Order Mennonite patients carrying a homozygous STRADA deletion of exons 9-13, and five additional PMSE patients with loss-of-function variants had been reported before this case. The condition includes distinctive facial traits and severe developmental delay or intellectual disability.
A 2016 review of progressive myoclonus epilepsies (PMEs) notes that treatment is only symptomatic and that therapy targeting the underlying genetic aetiology is in its infancy. Traditional drugs for PMEs are valproate, clonazepam, and phenobarbital (or primidone), which may improve overall performance by decreasing generalised seizures and, to a lesser extent, myoclonic jerks. Newer drugs shown to be effective include piracetam, levetiracetam, topiramate, zonisamide, and possibly perampanel for Lafora disease. However, the available data on drug efficacy are mainly based on small series or anecdotal reports. Two prospective, randomised, double-blind studies of the novel SV2A ligand brivaracetam in genetically confirmed Unverricht-Lundborg patients produced disappointing results. Drugs known to aggravate myoclonus or myoclonic seizures—phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin—should be avoided.
A 2021 overview of neonatal seizures notes that neonatal epilepsies can be caused by mutations in genes including KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A, and SCN8A. The review discusses new possible therapeutic strategies for these conditions but provides no specific efficacy data for any drug in PMSE.
No controlled trials have been conducted for any drug specifically in PMSE. The evidence for treating the epilepsy and myoclonus in this syndrome is extrapolated from small series and anecdotal reports in other progressive myoclonus epilepsies. What is missing is any dedicated trial in PMSE patients, funding for such a trial, and a clear understanding of whether the STRADA mutation requires a different treatment approach from other PMEs.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Epileptic Disorders · 2016 · 54 citations
Myoclonus and seizures in progressive myoclonus epilepsies: pharmacology and therapeutic trials
AbstractGeneralized motor seizures, usually tonic-clonic, tonic-vibratory, myoclonic or clonic, and stimulus-sensitive/action myoclonus are typical features of progressive myoclonus epilepsies (PMEs). Despite the introduction of many anticonvulsants, the treatment of these symptoms, particularly myoclonus, remains challenging, due to the incomplete and often transitory effects of most drugs. Moreover, treatment is only symptomatic, since therapy targeting the underlying aetiology for these genetic conditions is in its infancy. Traditional antiepileptic drugs for the treatment of PMEs are valproate, clonazepam, and phenobarbital (or primidone). These drugs may improve the overall performance of PME patients by decreasing their generalized seizures and, to a lesser extent, their myoclonic jerks. Newer drugs which have been shown to be effective include piracetam, levetiracetam, topiramate, zonisamide, and possibly perampanel for Lafora disease. The potential of other drugs (such as L-triptophan and N-acetylcysteine) and procedures (such as vagal and deep brain stimulation) has also been discussed. The available data on the efficacy of drugs are mainly based on small series or anecdotal reports. Two prospective, randomized, double blind studies investigating the novel SV2A ligand, brivaracetam, in genetically confirmed Unverricht-Lundborg patients have been performed with disappointing results. When treating PMEs, particular care should be paid to avoid drugs known to aggravate myoclonus or myoclonic seizures, such as phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin. The emergency treatment of motor status, which often complicates the course of PMEs, consists of intravenous administration of benzodiazepines, valproate, or levetiracetam.
Brain Sciences · 2021 · 38 citations · open access
Neonatal Seizures: An Overview of Genetic Causes and Treatment Options
AbstractSeizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called ‘Neonatal Epilepsies’. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and ‘Ohtahara syndrome’ (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.
Homozygous missense STRADA mutation in a patient with polyhydramnios, megalencephaly and symptomatic epilepsy syndrome
AbstractHomozygous or compound heterozygous mutations in STRADA cause polyhydramnios, megalencephaly and symptomatic epilepsy syndrome (PMSE), with additional features of distinctive facial traits and severe developmental delay or intellectual disability. This syndrome was first defined in 16 Old Order Mennonite patients, carrying a homozygous STRADA deletion of exon 9-13. Five additional PMSE patients have been reported since, each of them with loss-of-function variants. We report a female patient with the typical clinical features of PMSE, homozygous for a novel STRADA missense mutation c.792T>A (p.Ser264Arg) in exon 10. This finding contributes to the further delineation of the phenotype of PMSE.
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.
