DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lissencephaly type 3 — 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 moduleLissencephaly type 3 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 lissencephaly type 3 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 alpha 1a (TUBA1A) — TUBA1A 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 9WD9 · 2.26 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
Ten patients with lissencephaly were examined by magnetic resonance imaging in 1991. Six were under one year old at the time of their most recent examination. Those old enough for developmental assessment were, with a single exception, severely developmentally delayed. All patients had anatomical features compatible with impaired neuronal migration but normal myelination and, consequently, adequate glial migration. The severity of the lissencephaly did not seem to correlate with the severity of the clinical manifestations. One patient showed less delayed development than anticipated, perhaps because the most severely involved region of the brain was the prefrontal area.
A 2009 retrospective study of 63 patients with posteriorly predominant lissencephaly found that 40 carried either LIS1 point mutations (77.5%) or small genomic deletions (20%), and one carried a somatic nonsense mutation. Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with 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. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). 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. Neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly.
A 2003 sonographic evaluation describes lissencephaly as a neural disorder characterised by lack of sulcations in the brain, caused by an insult to the fetus early in gestation. Sonographic findings include agenesis of the corpus callosum, dilated third ventricle, and lack of sulcations. Patients diagnosed with lissencephaly do not usually develop intellectually past the three- to five-month age level.
No drug treatment is mentioned in any of these abstracts. What is missing for any potential repurposing effort is a molecular target or pathway known to be druggable in lissencephaly type 3, any preclinical model showing drug effect on neuronal migration, and any clinical trial design that could measure a meaningful change in developmental outcome or seizure control. Patient stratification by genotype and severity grade would be needed before any intervention could be tested.
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 · 1991 · 142 citations
The spectrum of lissencephaly: Report of ten patients analyzed by magnetic resonance imaging
AbstractClinical data and magnetic resonance imaging scans from 10 patients with lissencephaly were reviewed. Although 6 of the 10 patients were less than 1 year old at the time of their most recent examination, those who were old enough for developmental assessment were, with a single exception, severely developmentally delayed. All patients had anatomical features compatible with impaired neuronal migration but normal myelination and, consequently, adequate glial migration. The severity of the lissencephaly did not seem to correlate with the severity of the clinical manifestations. One patient showed less delayed development than anticipated, perhaps because the most severely involved region of the brain was the prefrontal area.
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.
Journal of diagnostic medical sonography · 2003 · 0 citations
The Sonographic Evaluation of Lissencephaly
AbstractLissencephaly is a neural disorder characterized by lack of sulcations in the brain. In lissencephaly, the normal migration of the neuron does not occur due to an insult to the fetus early in gestation. This causes a “smooth brain” appearance. Lissencephaly is associated with syndromes such as Walker-Warburg and Miller-Dieker syndromes. Sonographic findings of lissencephaly include agenesis of the corpus collosum, dilated third ventricle, and lack of sulcations. Patients diagnosed with lissencephaly do not usually de-velop intellectually past the three- to five-month age level.
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.
