DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lissencephaly spectrum disorders — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLissencephaly spectrum disorders maps to a 8-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 lissencephaly spectrum disorders 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 gamma 1 (TUBG1) — TUBG1 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3CB2 · 2.303 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Lissencephaly is a spectrum of severe brain malformations caused by failure of migrating neurons to reach optimal positions in the developing cerebral cortex. The genetic basis involves several identified genes, most notably LIS1 and DCX. In the largest reported data set of 63 patients with posteriorly predominant lissencephaly, 40 carried LIS1 point mutations (77.5%) or small genomic deletions (20%), and one carried a somatic nonsense mutation. Among those with LIS1 mutations, most showed posterior agyria (grade 3a, 55.3%), thin corpus callosum (50%), and prominent perivascular spaces (67.4%). Patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. Tetraplegia occurred in 61.1% of LIS1 patients, 82.9% had early onset of seizures, and 48.7% had seizures more often than daily. Neither mutation type nor location predicted severity of LIS1-related lissencephaly.
A 2006 case report describes a patient with lissencephaly in whom fluorescence in situ hybridization and DCX mutation analysis determined the etiologic diagnosis, allowing precise genetic counseling and prenatal diagnosis for the family. The parents had normal genetic makeup, indicating a de novo mutation. A 2022 case report describes a 12-year-old child with type II lissencephaly, chronic epilepsy, and behavioural disturbances managed with divalproex sodium and clobazam. This is a single case, not a trial, and reports management of symptoms rather than modification of the underlying brain malformation.
No drug has been shown in any of these abstracts to alter the course of lissencephaly itself. The 2022 case report describes symptomatic seizure control in one patient, but no controlled data exist. What is missing is any preclinical or clinical research aimed at correcting the underlying neuronal migration defect, any trial design for a disease-modifying intervention, and any patient stratification beyond genetic diagnosis that could guide such an effort. Funding for basic research into neuronal migration mechanisms and for development of animal models that might support drug screening remains absent from the published record.
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 Medical Genetics Part C Seminars in Medical Genetics · 2014 · 111 citations
The genetics of lissencephaly
AbstractLissencephaly is a spectrum of severe brain malformations caused by the failure of migrating neurons to reach optimal positions in the developing cerebral cortex. Several syndromes associated with lissencephaly have been characterized in recent years. Identification of the genetic basis of these disorders has brought fascinating insights into the mechanisms of brain development, as well as benefits to patients through improved molecular diagnosis and genetic counseling. This review explores the clinical presentation, radiological features, histological findings and molecular basis of lissencephaly with the aim of facilitating the selection and interpretation of gene tests in patients with 'smooth brain' phenotypes.
Archives of Neurology · 2009 · 100 citations · open access
LIS1-Related Isolated Lissencephaly
AbstractOBJECTIVE: With the largest data set of patients with LIS1-related lissencephaly, the major cause of posteriorly predominant lissencephaly related to either LIS1 mutation or intragenic deletion, described so far, we aimed to refine the spectrum of neurological and radiological features and to assess relationships with the genotype. DESIGN: Retrospective study. Subjects A total of 63 patients with posteriorly predominant lissencephaly. INTERVENTIONS: Of the 63 patients, 40 were found to carry either LIS1 point mutations (77.5%) or small genomic deletions (20%), and 1 carried a somatic nonsense mutation. On the basis of the severity of neuromotor impairment, epilepsy, and radiological findings, correlations with the location and type of mutation were examined. RESULTS: Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with thin corpus callosum (50%) and prominent perivascular spaces (67.4%). By contrast, patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). Conversely, the severity of epilepsy was not determined with the same reliability because 82.9% had early onset of seizures and 48.7% had seizures more often than daily. In addition, neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly. CONCLUSION: Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations.
Medical Science · 2022 · 0 citations · open access
Type II Lissencephaly with chronic epilepsy and behavioral disturbances: A rare case report
AbstractLissencephaly is a rare genetic disorder of brain malformation. It is characterized by the absence of normal folds or convolutions of the cerebral cortex. It is caused by abnormal neuronal migration during a period of embryonic development. It has various symptoms such as difficulty in swallowing, unusual facial appearance, abnormal muscular spasms, failure to thrive, extreme psychomotor retardation, deformities of fingers, toes, or hands, intellectual disability, and the seizure episodes. There are two variants of Lissencephaly namely type I and II. This case report has highlighted a rare case of type II Lissencephaly with chronic epilepsy and behavioral disturbances in a 12-year-old child managed effectively with a mood stabilizing antiepileptic drug named Divalproex sodium and a benzodiazepine named Clobazam.
Indian journal of human genetics · 2006 · 0 citations
Lissencephaly child showing FISH negative and mutation in DCX gene with normal parental genetic makeup
AbstractLissencephaly is a clinically and genetically heterogeneous malformation of the brain, leading to a severe disabling condition and seizures. The recent discovery of molecular techniques and identification of lissencephaly genes (LIS 1 and DCX) has allowed etiologic diagnosis of this disorder. We describe a patient with lissencephaly in whom fluorescence in situ hybridization and DCX mutation analysis determined etiologic diagnosis, allowing precise genetic counseling and providing prenatal diagnosis for the family.
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.
