DeCure for Developmental and epileptic encephalopathy 93
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy 93 — 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 moduleDevelopmental and epileptic encephalopathy 93 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
No approved-drug candidate for developmental and epileptic encephalopathy 93 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
ATPase H+ transporting V1 subunit A (ATP6V1A) — ATP6V1A 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 6WLZ · 2.9 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Developmental and epileptic encephalopathy 93 is one of the severe early-onset epilepsies covered by the general reviews. The 2021 review states that many DEEs are related to gene variants, onset is typically in early childhood, and neurocognition may benefit from some precision therapies but is not improved by seizure control alone. The 2018 review is blunt: most antiseizure drugs are ineffective in these disorders, treatments that are effective often carry significant risk and cost, and most patients experience very poor outcomes, though a significant minority respond to or are cured by specific therapies.
Two single-gene case reports show specific drug responses. A 2022 report on SLC13A5-epilepsy describes a child with a novel homozygous loss-of-function mutation and an extremely severe neonatal presentation with drug-resistant seizures and burst-suppression EEG. Early carbamazepine use resulted in dramatic improvement both clinically and on EEG, with follow-up to age 4 years. A 2024 report on SCN8A-DEE describes a 4-month-old girl with intractable epilepsy in whom most antiepileptic drugs were ineffective, but high-dose phenytoin suppressed seizures. After targeted DNA sequencing revealed a pathogenic Val1315Met variant, combination therapy with sodium channel blockers resolved seizures entirely. The authors note that even when a single sodium channel blocker is insufficient, combination therapy can lead to seizure freedom in SCN8A-DEE.
A 2013 surgical series on children with destructive encephalopathy and medically intractable seizures included 48 patients, of whom 27 underwent resective and 21 palliative surgery. Sixteen patients (33.3%) became seizure-free, and 27 parents (87.5%) reported satisfaction with the outcome. Among parents whose children were not seizure-free, 14 (77.8%) reported satisfaction with improvement in cognitive and behavioural issues. Hypoxic-ischaemic injury was the most common underlying cause.
What is still missing for DEE93 specifically are prospective trials, any systematic data on patient stratification by genotype, and funding to move beyond single-case reports. The 2018 review notes that next-generation sequencing has revolutionised gene identification but has had only modest impact on patient-specific treatment decisions. No abstract provides survival or response rates for DEE93 as a named entity.
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 · 2021 · 126 citations · open access
Developmental and epileptic encephalopathies: recognition and approaches to care
AbstractThe term "developmental and epileptic encephalopathy" (DEE) refers to when cognitive functions are influenced by both seizure and interictal epileptiform activity and the neurobiological process behind the epilepsy. Many DEEs are related to gene variants and the onset is typically during early childhood. In this setting, neurocognition, whilst not improved by seizure control, may benefit from some precision therapies. In patients with non-progressive diseases with cognitive impairment and co-existing epilepsy, in whom the epileptiform activity does not affect or has minimal effect on function, the term "developmental encephalopathy" (DE) can be used. In contrast, for those patients with direct impact on cognition due to epileptic or epileptiform activity, the term "epileptic encephalopathy" (EE) is preferred, as most can revert to their normal or near normal baseline cognitive state with appropriate intervention. These children need aggressive treatment. Clinicians must tailor care towards individual needs and realistic expectations for each affected person; those with DE are unlikely to gain from aggressive antiseizure medication whilst those with EE will gain. Patients with DEE might benefit from a precision medicine approach in order to reduce the overall burden of epilepsy.
Epileptic encephalopathies: Optimizing seizure control and developmental outcome
AbstractCognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes.
CONTINUUM Lifelong Learning in Neurology · 2018 · 15 citations
Epileptic Encephalopathies
AbstractPURPOSE OF REVIEW: This article reviews the manifestations and treatment of the epileptic encephalopathies, which are a heterogeneous group of disorders characterized by both seizures and neurocognitive impairment. RECENT FINDINGS: Next-generation (exome- and genome-based) sequencing technologies are revolutionizing the identification of single-gene causes of epileptic encephalopathy but have only had a modest impact on patient-specific treatment decisions. The treatment of most forms of epileptic encephalopathy remains a particularly challenging endeavor, with therapeutic decisions chiefly driven by the electroclinical syndrome classification. Most antiseizure drugs are ineffective in the treatment of these disorders, and treatments that are effective often entail significant risk and cost. SUMMARY: The epileptic encephalopathies continue to pose a major challenge in diagnosis and treatment, with most patients experiencing very poor outcomes, although a significant minority of patients respond to, or are even cured by, specific therapies.
Journal of Epilepsy Research · 2013 · 7 citations · open access
Epilepsy Surgery in Pediatric Intractable Epilepsy with Destructive Encephalopathy
AbstractBACKGROUND AND PURPOSE: The aim of the current study is to review the clinical features, surgery outcomes and parental satisfaction of children with destructive encephalopathy who underwent epilepsy surgery due to medically intractable seizures. METHODS: 48 patients who underwent epilepsy surgery from October 2003 to August 2011 at Severance Children's Hospital have been reviewed. The survey was conducted for functional outcomes and parental satisfaction at least 1 year after the surgery. RESULTS: Epileptic encephalopathy including Lennox-Gastaut syndrome and infantile spasms was more prevalent than symptomatic focal epilepsy. Hypoxic ischemic injury accounted for most of the underlying etiology of the destructive encephalpathy, followed by central nervous system infection and head trauma. 27 patients (56.3%) underwent resective surgery and 21 patients (43.7%) underwent palliative surgery. 16 patients (33.3%) achieved seizure free and 27 parents (87.5%) reported satisfaction with the outcome of their children's epilepsy surgery. In addition, 14 parents (77.8 %) whose children were not seizure free reported satisfaction with their children's improvement in cognitive and behavior issues. CONCLUSIONS: Epilepsy surgery in destructive encephalopathy was effective for controlling seizures. Parents reported satisfaction not only with the surgical outcomes, but also with improvement of cognitive and behavior issues.
Annals of Clinical and Translational Neurology · 2022 · 5 citations · open access
Carbamazepine efficacy in a severe electro‐clinical presentation of <scp><i>SLC13A5</i></scp>‐epilepsy
AbstractRecessive mutations in the SLC13A5 gene encoding the sodium-dependent citrate transporter are a recently identified cause of developmental and epileptic encephalopathy. Here, we describe a child harboring a novel homozygous loss-of-function mutation in the SLC13A5 gene (c.1496C>T-p.Ser499Phe) and exhibiting an unusual extremely severe neonatal presentation with drug-resistant seizures and burst-suppression EEG pattern. Early carbamazepine use resulted in dramatic improvement both clinically and on EEG features. Follow-up from the neonatal period to the age of 4 years is documented. This case expands the electro-clinical phenotype associated with SLC13A5-related disease and confirms the efficacy and safety of carbamazepine in nonstructural early-onset epilepsies.
Brain and Development Case Reports · 2024 · 2 citations · open access
A case of SCN8A-related developmental epileptic encephalopathy diagnosed by clinical speculation driven targeted DNA sequencing and remission of epilepsy by sodium channel blockers combination therapy
AbstractSCN8A-related epilepsy and/or neurodevelopmental disorders encompass a very broad spectrum of phenotypes. The most severe form, SCN8A developmental and epileptic encephalopathy (DEE), develops intractable epilepsy from early infancy and can lead to sudden death. Early diagnosis and therapeutic intervention are essential, but diagnosis is based on genetic testing and definitive diagnosis is often delayed. A 4-month-old girl presented with intractable epilepsy. Most antiepileptic drugs were ineffective, but high doses of phenytoin suppressed seizures, so a sodium channelopathy was suspected and targeted DNA sequencing was performed, which revealed a pathogenic missense variant Val1315Met in the SCN8A gene. Based on the diagnosis, combination therapy with sodium channel blockers (SCBs) was initiated and the seizures resolved. We experienced SCN8A-DEE, which led to early diagnosis based on clinical course and improved prognosis. It is noteworthy that even when the effect of a single SCB is insufficient, as in this case, combination therapy can lead to seizure free in SCN8A-DEE.
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.
