DeCure for Complex cortical dysplasia with other brain malformations 5
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for complex cortical dysplasia with other brain malformations 5 — 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 moduleComplex cortical dysplasia with other brain malformations 5 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 complex cortical dysplasia with other brain malformations 5 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
tubulin beta 2A class IIa (TUBB2A) — TUBB2A 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 7NVN · 3.0 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
In a series of 126 patients with malformations of cortical development selected from 321 consecutively operated patients, the largest group was 81 individuals with focal cortical dysplasia. Among these, 42 had architectural dysplasia, 12 had cytoarchitectural dysplasia, and 27 had Taylor's focal cortical dysplasia. After at least one year of follow-up, 69% of patients with Taylor's type dysplasia were seizure-free (Engel class Ia), compared with 45% of cytoarchitectural dysplasia and 49% of architectural dysplasia patients. The series also included nine patients with periventricular heterotopia, three with polymicrogyria, one with hemimegalencephaly, and one with subcortical band heterotopia. Magnetic resonance imaging was unhelpful in 17 of 81 patients with focal cortical dysplasia and in seven of 31 with neuronal heterotopia.
Analysis of layer-specific gene expression in cortical samples from patients with temporal lobe epilepsy found that architectural dysplasia and temporal lobe sclerosis (a variant of architectural dysplasia) showed alterations mainly involving layers V and VI, highlighted by altered distribution of ER81- and NURR1-positive cells. Atypical coexpression of NURR1 and CUX2 mRNA was detected in neurons making up small lentiform nodules in white matter. These findings suggest defects in cortical organisation involving deeper cortical neurons may be a common mechanism in these dysplasia subtypes, whether isolated or associated with hippocampal sclerosis.
A father and daughter displayed strictly similar focal brain dysplasia characterised by regional medial posterior laminar subcortical grey matter heterotopia. LIS1 and DCX gene defects were excluded. No family presenting such anomalies had been described before 2003.
What is still missing is systematic genetic screening beyond LIS1 and DCX in familial cases, prospective surgical outcome data stratified by molecular pathology, and any pharmacological intervention tested in these specific malformation subtypes. No drug treatment is reported 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.
Epileptic Disorders · 2003 · 45 citations · open access
Focal cortical resection in malformations of cortical development
AbstractMalformations of cortical development may be associated with drug-resistant partial epilepsy suitable for surgical therapy. From the anatomopathological point of view, this categorisation has been used in reference to a wide range of alterations of the cortical mantle. Focal cortical dysplasias represent the main group of malformations of cortical development, but there are also other types of alterations, such as heterotopias, double cortex or polymicrogyria. Defining candidacy for surgical therapy and tailored resection requires thorough pre-surgical evaluation so that the approach will be individualised for each patient. We present our series of 126 patients with malformation of cortical development selected from 321 consecutively operated patients. Within this group encompassing different types of malformation of cortical development, including periventricular heterotopia (nine patients), polymicrogyria (three patients), hemimegalencephaly (one patient) and subcortical band heterotopia (one patient), the largest group was 81 individuals with focal cortical dysplasia. For this last group, we propose a simplified classification defining 42 architectural dysplasias, 12 cytoarchitectural dysplasias and 27 Taylor's focal cortical dysplasias. In addition, at routine neuropathological investigation, the only morphological alteration shown by 31 patients was diffuse neuronal heterotopia. All patients underwent scalp EEG and video-EEG, and 75 patients (59.5%) also underwent stereo-EEG. Magnetic resonance imaging and stereotactic stereoscopic angiography represented the indispensable premises for further studies, in particular stereo-EEG, and for planning surgery and tailoring resection. Magnetic resonance imaging was unhelpful in 17 out of 81 patients with focal cortical dysplasia and in seven out of 31 with neuronal heterotopia, while signal alterations were present in all other cases. Common characteristics corresponding to clinical-histopathological homogeneous subgroups were found within the focal cortical dysplasia group. In patients with architectural dysplasia, the epileptogenic zone was mainly in the temporal lobe and there was a lower seizure frequency than in patients with Taylor's focal cortical dysplasia. Patients with Taylor's type had an epileptogenic zone that was mainly extra-temporal, and a distinctive interictal stereo-EEG. The best outcome was observed in patients with Taylor's type dysplasia: 69% seizure-free (Engel class Ia) after at least 1 year of follow-up, compared with 45% of cytoarchitectural dysplasia and 49% of architectural dysplasia patients.
Altered layer-specific gene expression in cortical samples from patients with temporal lobe epilepsy
AbstractPURPOSE: Neuropathologic investigations frequently reveal the presence of architectural cortical dysplasia in patients with temporal lobe epilepsy (TLE), sometimes as an isolated finding but more commonly associated with hippocampal sclerosis (HS) and white matter abnormalities. The histologic pattern and the developmental origin of these alterations are not clear, and their diagnostic criteria are poorly defined. The aim of this study was to investigate the expression patterns of layer-specific genes in cortical specimens from patients with TLE presenting different subtypes of cortical malformations in order to elucidate the disorganization of the laminar architecture of such epileptogenic abnormalities and provide evidence to enable a more objective neuropathologic diagnosis. METHODS: We analyzed the expression patterns of CUX2, RORBETA, ER81, NURR1, and CTGF genes, respectively specific markers of layers II-III, IV, V, VI, and VIb, in surgical samples by means of in situ hybridization and compared them with those observed in control cortices. The pathologic samples included typical architectural dysplasia (group 1); temporal lobe sclerosis, a variant of architectural dysplasia (group 2); and white matter heterotopic neuronal aggregates, namely small lentiform nodules (group 3). These abnormalities may have been associated or not with HS. KEY FINDINGS: All of the genes had a laminar expression pattern in normal cortices, whereas groups 1 and 2 showed alterations mainly involving layers V and VI, and highlighted by the altered distribution of ER81- and NURR1-positive cells. The expression of ER81 and NURR1 genes was different among the groups, and atypical coexpression of NURR1 and CUX2 mRNA was detected in the neurons making up the small lentiform nodules. SIGNIFICANCE: These findings indicate that defects in cortical organization involving the deeper cortical neurons may be a common etiopathogenic mechanism in group 1 and 2 cortical dysplasia, whether isolated or associated with HS, and that developmental disorders may also be present in the white matter (group 3). They also provide evidence that the layer-specific genes can be usefully used to investigate the neuropathology of human cortical dysplasia.
Familial Bilateral Medial Parietooccipital Band Heterotopia not Related to DCX or LIS1 Gene Defects
AbstractA father and his daughter displayed strictly similar focal brain dysplasia at MR examination, characterized by regional medial posterior laminar sub-cortical grey matter heterotopia. To our knowledge, no family presenting such anomalies has yet been described. LIS1 and DCX gene defects were excluded. Collecting patients with such inherited dysplasia should improve our knowledge of the genetic basis of cortical malformations.
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.
