DeCure for Complex cortical dysplasia with other brain malformations 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for complex cortical dysplasia with other brain malformations 1 — screening already-approved drugs against its 4-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 1 maps to a 4-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 1 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 3 class III (TUBB3) — TUBB3 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6S8L · 1.801 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
The 2011 study examined layer-specific gene expression in cortical samples from patients with temporal lobe epilepsy. It analysed CUX2, RORBETA, ER81, NURR1, and CTGF genes in surgical samples. In normal cortices all genes showed a laminar expression pattern. In two groups of pathological samples — typical architectural dysplasia and temporal lobe sclerosis — alterations mainly involved 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 white matter heterotopic nodules. The authors concluded that defects in deeper cortical organisation may be a common mechanism in those dysplasia subtypes.
A 2003 report described a father and daughter with strictly similar focal brain dysplasia on MRI, characterised by regional medial posterior laminar subcortical grey matter heterotopia. LIS1 and DCX gene defects were excluded. The authors noted that no family with such anomalies had been described before and that collecting more patients should improve knowledge of the genetic basis of cortical malformations.
A 2007 chapter stated that malformations of cortical development are increasingly recognised as a relatively common cause of refractory epilepsy, mental retardation, and other neurological disorders. It highlighted that the molecular and genetic bases of many cortical malformations have been elucidated, including disorders of microcephaly, grey matter heterotopia, lissencephaly syndromes, and polymicrogyria.
A 2023 case report described a young girl with drug-resistant epilepsy who was on two medicines and underwent surgery. Histopathological examination revealed focal cortical dysplasia. The report stated that focal cortical dysplasia is responsible for nearly half of intractable epilepsy cases in children and adults and is characterised by quite good treatment outcome. No drug treatment for the underlying dysplasia was tested or proposed in any of these abstracts. What remains missing is any controlled trial of a pharmacological intervention, any validated biomarker to stratify patients by molecular subtype, and the funding to move from descriptive gene-expression studies to mechanism-based therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Roentgenology · 2011 · 54 citations
Bottom-of-Sulcus Dysplasia: Imaging Features
AbstractOBJECTIVE: Dysplasia at the bottom of a sulcus is a subtle but distinct malformation of cortical development relevant to epilepsy. The purpose of this study was to review the imaging features important to the clinical diagnosis of this lesion. MATERIALS AND METHODS: All cases recognized as typical bottom-of-sulcus dysplasia in our comprehensive epilepsy program over the period 2002-2007 were included in the study. RESULTS: In the 20 cases recognized, three major features were identified: cortical thickening at the bottom of a sulcus; a funnel-shaped extension of the lesion toward the ventricular surface, commonly with abnormal signal intensity; and an abnormal gyral pattern related to the bottom-of-sulcus dysplasia, sometimes with a puckered appearance. The pathologic features of the resected lesions were typical of focal cortical dysplasia. CONCLUSION: Bottom-of-sulcus dysplasia is a distinctive malformation of cortical development that can be diagnosed on the basis of imaging characteristics. Reliable identification of this type of malformation of cortical development is difficult but clinically important because the lesion appears to be highly epileptogenic and because the prognosis for seizure control is excellent after focal resection.
Malformations of cortical development in neurofibromatosis type 1
AbstractThe authors report three patients with neurofibromatosis type 1 and different types of malformations of cortical development: Patient 1 had a possible transmantle cortical dysplasia involving the right temporoinsuloparieto-occipital areas; Patient 2 had a periventricular band of heterotopic gray matter with an overlying pachygyric cerebral cortex; and Patient 3 had a left perisylvian polymicrogyria. Because all of these lesions result from different pathogenetic mechanisms, neurofibromin may play a role during several stages of cortical development.
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.
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.
The Genetic Basis of Human Cerebral Cortical Malformations
AbstractMalformations of cortical development occur when the normal process of brain development is disrupted. With the widespread use of high-resolution neuroimaging, brain malformations are increasingly being recognized as a relatively common cause orefractory epilepsy, mental retardation, and other neurological disorders. The molecular and genetic bases of many cortical malformations have been elucidated in recent years, both expanding our understanding of the underlying biological processes in brain development and informing our approach to these disorders in clinical practice. This chapter highlights some of these malformations, including disorders of microcephaly, gray matter hetero-topia, lissencephaly syndromes, and polymicrogyria.
Bangladesh Journal of Neurosurgery · 2023 · 0 citations · open access
Drug-resistant Focal Epilepsy due to Focal Cortical Dysplasia: A Case Report
AbstractFocal cortical dysplasias (FCDs) belong to the large spectrum of malformations of cortical development (MCDs) and represent the most common structural brain lesion in children with drug-resistant focal epilepsies submitted to surgical treatment. It is responsible for nearly half of intractable epilepsy cases in children and adults, and at the same time it is characterized by quite good treatment outcome. We describe a case where a young girl had been suffering from intractable epilepsy and was on two medicines. She was operated upon and was relieved of her symptoms. Her histopathological examination revealed focal cortical dysplasia. We have to keep in mind that FCD can present as low grade glioma and treat it carefully. Bang. J Neurosurgery 2022; 12(1): 24-28
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.
