DeCure for Cortical dysplasia-focal epilepsy syndrome
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for cortical dysplasia-focal epilepsy syndrome — 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 moduleCortical dysplasia-focal epilepsy syndrome 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 cortical dysplasia-focal epilepsy syndrome 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
contactin associated protein 2 (CNTNAP2) — CNTNAP2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5Y4M · 1.31 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2015 study of seven patients from four families with DEPDC5 mutations and focal epilepsy associated with focal cortical dysplasia, all had drug-resistant focal epilepsy. Five underwent surgery and one had a brain biopsy. Histopathology confirmed FCD IIa in two patients (including one whose MRI had been negative), showed FCD I in two others, and was inconclusive in the remaining two. After surgery, three patients became seizure-free and one had a worthwhile improvement. Sequencing of blood DNA found truncating DEPDC5 mutations in all four families; one mutation was mosaic in an asymptomatic father. A brain somatic DEPDC5 mutation was identified in one patient in addition to the germline mutation. The authors concluded that germline, germline mosaic, and brain somatic DEPDC5 mutations may cause epilepsy associated with FCD, and that epilepsy surgery is a valuable alternative for drug-resistant DEPDC5-positive focal epilepsies even when MRI is unremarkable.
A 2003 prospective three-year study investigated how family history of epilepsy affects age at onset in patients with focal cortical dysplasia, but the abstract provided does not give numerical results or a clear conclusion. Other abstracts from 2013 and 2011 describe FCD as a major cause of pharmaco-resistant focal epilepsy often requiring neurosurgery, and note that FCD type II (Taylor) and type I are distinct entities with different aetiologies, but they offer no new clinical trial data.
What is still missing is a prospective trial testing any drug specifically in DEPDC5-mutation-positive focal cortical dysplasia, a clear understanding of whether mTOR inhibitors such as everolimus can reduce seizure frequency in this genetically defined subgroup, and systematic stratification of patients by germline versus somatic mutation status. The surgical data come from only seven patients, and no randomised controlled trial has been conducted.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 2015 · 286 citations
Familial focal epilepsy with focal cortical dysplasia due to <scp><i>DEPDC</i></scp><i>5</i> mutations
AbstractOBJECTIVE: The DEPDC5 (DEP domain-containing protein 5) gene, encoding a repressor of the mTORC1 signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies. We aimed to further extend the role of DEPDC5 to focal cortical dysplasias (FCDs). METHODS: Seven patients from 4 families with DEPDC5 mutations and focal epilepsy associated with FCD were recruited and investigated at the clinical, neuroimaging, and histopathological levels. The DEPDC5 gene was sequenced from genomic blood and brain DNA. RESULTS: All patients had drug-resistant focal epilepsy, 5 of them underwent surgery, and 1 had a brain biopsy. Electroclinical phenotypes were compatible with FCD II, although magnetic resonance imaging (MRI) was typical in only 4 cases. Histopathology confirmed FCD IIa in 2 patients (including 1 MRI-negative case) and showed FCD I in 2 other patients, and remained inconclusive in the last 2 patients. Three patients were seizure-free postsurgically, and 1 had a worthwhile improvement. Sequencing of blood DNA revealed truncating DEPDC5 mutations in all 4 families; 1 mutation was found to be mosaic in an asymptomatic father. A brain somatic DEPDC5 mutation was identified in 1 patient in addition to the germline mutation. INTERPRETATION: Germline, germline mosaic, and brain somatic DEPDC5 mutations may cause epilepsy associated with FCD, reinforcing the link between mTORC1 pathway and FCDs. Similarly to other mTORopathies, a "2-hit" mutational model could be responsible for cortical lesions. Our study also indicates that epilepsy surgery is a valuable alternative in the treatment of drug-resistant DEPDC5-positive focal epilepsies, even if the MRI is unremarkable.
In Focal Cortical Dysplasia, Family History of Epilepsy Affects Onset Age
AbstractSince Taylor first described focal cortical dysplasia (FCD) in 1971 ( Neurol Neurosurg Psychiatry 1971; 34:369), interest in this pathology has increased, especially because FCD has been identified as a cause of intractable (drug-refractory) epilepsy. With advances in neuroimaging and epilepsy surgery, we are more able to identify and treat intractable epilepsy in patients with FCD. In this prospective 3-year study, the authors investigated the contribution of …
German Medical Science (German Research Foundation) · 2013 · 0 citations · open access
Balloon cells in the epileptogenic human cortex of focal cortical dysplasia type 2b
AbstractObjective: Focal cortical dysplasia (FCD), a malformation of cerebrocortical development, is regarded as a major cause of pharmaco-resistant focal epilepsy thus frequently becoming object to neurosurgical treatment. Severe focal cortical dysplasia (FCD 2b) is characterized by distinct cortical dyslamination,[for full text, please go to the a.m. URL]
AbstractAbnormalities of cortical development are frequent causes of refractory epilepsy. Among these pathologies, focal cortical dysplasia (FCD) is a heterogeneous group of disorders pathologically characterized by loss of normal cortical structure. Two distinct entities with different etiology have been described (FCD type I and FCD type II Taylor). This study presents relevant case studies, highlighting the pathological features in magnetic resonance imaging.
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.
