DeCure for Complex cortical dysplasia with other brain malformations 6
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for complex cortical dysplasia with other brain malformations 6 — 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 6 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 6 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 class I (TUBB) — TUBB 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 7TTT · 2.9 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts do not name a specific drug for complex cortical dysplasia with other brain malformations 6. One PhD project from 2021 states that there are currently no pharmacological treatments for diffuse malformations of cortical development, and that the aim of that work was to assess the effectiveness of novel in vitro treatment for mTOR pathway related MCDs, but no results from that assessment are provided in the abstract. The 2012 review updates a classification for malformations of cortical development but does not report any drug trial.
Surgical resection is described in two abstracts. In a 2003 series of 126 patients with malformations of cortical development who underwent focal cortical resection, 81 had focal cortical dysplasia. Among those, the best outcome was in patients with Taylor's type dysplasia: 69% were seizure-free (Engel class Ia) after at least one year of follow-up, compared with 45% for cytoarchitectural dysplasia and 49% for architectural dysplasia. A 2018 prospective trial of ultrasound-assisted surgery for focal cortical dysplasia in therapy-refractory epilepsy is mentioned but the full text is not available in the given abstract.
A 2003 case report describes a girl with an unusual form of subcortical band heterotopia, simplified gyral pattern, syndactyly, and other congenital anomalies. She had severe developmental delay and epilepsy at age one. Chromosome studies and mutation analysis of DCX and LIS1 were negative. The 2011 study of layer-specific gene expression in temporal lobe epilepsy samples found that defects in cortical organisation involving deeper cortical neurons may be a common mechanism in certain dysplasia groups, but no treatment is discussed.
What is still missing is any clinical trial of a drug for this specific condition, any validated molecular target for therapy, and any patient stratification beyond surgical candidacy. The genetic heterogeneity of these malformations is acknowledged, but functional validation of variants and in vitro treatment assessment remain at the research stage without published efficacy data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 2012 · 1076 citations · open access
A developmental and genetic classification for malformations of cortical development: update 2012
AbstractMalformations of cerebral cortical development include a wide range of developmental disorders that are common causes of neurodevelopmental delay and epilepsy. In addition, study of these disorders contributes greatly to the understanding of normal brain development and its perturbations. The rapid recent evolution of molecular biology, genetics and imaging has resulted in an explosive increase in our knowledge of cerebral cortex development and in the number and types of malformations of cortical development that have been reported. These advances continue to modify our perception of these malformations. This review addresses recent changes in our perception of these disorders and proposes a modified classification based upon updates in our knowledge of cerebral cortical development.
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.
American Journal of Medical Genetics Part A · 2003 · 8 citations
Subcortical band heterotopia with simplified gyral pattern and syndactyly
AbstractWe describe a girl with an unusual form of subcortical band heterotopia (SBH) and a complex malformation syndrome. SBH had an irregular inner margin, organized in contiguous fascicles of migrating neurons, sometimes giving the appearance of many small contiguous gyri. The true cortex had decreased thickness and showed a simplified gyral pattern with decreased number of gyri, which were usually of increased width, and shallow sulci. The cerebellum was hypoplastic. Additional features included epicanthal folds, hypertelorism, small nose with hypoplastic nares, bilateral syndactyly of the toes, pulmonary valve stenosis, atrial and ventricular septal defects. At the age of 1 year the patient had severe developmental delay and epilepsy. Chromosome studies and mutation analysis of the DCX and LIS1 genes gave negative results. This observation delineates a new multiple congenital abnormalities mental retardation syndrome and confirms genetic heterogeneity of SBH.
German Medical Science (German Research Foundation) · 2018 · 0 citations · open access
Ultrasound-assisted surgery for focal cortical dysplasia in patients with therapy-refractory epilepsy – a single center prospective trial
AbstractObjective: Recent advances in neuroimaging, especially postprocessing MRI analysis, allow to detect malformations of cortical development (MCDs) as the underlying pathology of focal epileptogenesis, of which focal cortical dysplasia (FCDs) is the most frequent subtype. Surgery has shown to be the best[for full text, please go to the a.m. URL]
German Medical Science (German Research Foundation) · 2012 · 0 citations · open access
Structural, cellular and molecular characterization of focal cortical dysplasia
AbstractObjective: Focal cortical dysplasia (FCD) is considered as a local, neocortical malformation. FCD are a major cause of pharmaco-resistant focal epilepsy and thus are frequently object of neurosurgical resection. However, little is known about the related histopathologic and molecular phenotypes underlying[for full text, please go to the a.m. URL]
Premio Tesi dottorato/Premio Tesi di dottorato · 2021 · 0 citations · open access
Functional validation of genetic variants identified by next generation sequencing in malformations of cortical development
AbstractMalformations of cortical development (MCDs) result from a disruption in the process of the human brain cortex formation: currently, there are no pharmacological treatments for diffuse MCDs. Next-generation sequencing has accelerated the identification of MCDs causing genes: in some cases, functional studies are needed to clarify the role of genetic variants. The aim of this PhD project has been to apply a multidisciplinary approach to identify causative mutations in patients with MCDs, validate the pathogenic role of the identified mutations, and assess the effectiveness of novel in vitro treatment for mTOR pathway related MCDs.
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.
