DeCure for Lissencephaly type 1 due to doublecortin gene mutation
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lissencephaly type 1 due to doublecortin gene mutation — 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 1 due to doublecortin gene mutation 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 1 due to doublecortin gene mutation 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
doublecortin (DCX) — DCX 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 4ATU · 8.3 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
No drug treatment is tested, proposed, or mentioned in any of these abstracts. The three papers are genetic and descriptive: they define the doublecortin gene as an X-linked cause of type 1 lissencephaly in males and subcortical band heterotopia (double cortex) in females, and they distinguish it from the autosomal LIS1 gene. One abstract reports a cohort of 8 pedigrees and 47 sporadic patients with double cortex syndrome who were screened for doublecortin mutations, but no therapeutic intervention or outcome data are given. No survival rates, response rates, or sample sizes for any drug appear because no drug was studied.
The abstracts contain no evidence that any compound alters the course of lissencephaly or double cortex. The only actionable information is genetic: mutation analysis of LIS1 and doublecortin is recommended for determining aetiology and recurrence risk in families. The 2001 review notes that mouse modelling of these human disorders “holds promise” for understanding brain formation, but that promise has not yet produced a therapy in the data presented.
What is missing is any preclinical or clinical drug development programme, any trial design, any patient stratification strategy beyond genetic diagnosis, and any funding for therapeutic research. Without those, the abstracts offer only a genetic diagnosis, not a treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2000 · 59 citations
Classical lissencephaly and double cortex (subcortical band heterotopia): LIS1 and doublecortin
AbstractClassical lissencephaly and double cortex are genetic neuronal migration disorders associated with mental retardation and epilepsy. In classical lissencephaly, the six-layered cortex is replaced by a four layered structure lacking normal gyri or sulci. In double cortex, a second layer of cortical neurons underlies a normal cortex. A mutation in LIS1 or doublecortin can lead to either classical lissencephaly or double cortex, but because LIS1 is autosomal and doublecortin is X-linked (on the X chromosome), the disease inheritance pattern and risk of recurrence for the two genes are distinct. Mutation analysis for LIS1 and doublecortin is essential in determining the etiology of the disease in patients and may be helpful in determining the recurrence risk in families.
Current Opinion in Neurology · 2001 · 14 citations
Cerebral gyral dysplasias: molecular genetics and cell biology
AbstractThe promise of genetics has been partly realized in our understanding of human brain development as this relates to disorders of gyral formation. Cerebral gyral dysplasias are disorders of brain formation that result in phenotypes with the common feature of abnormal cerebral gyri. This review emphasizes the recent progress made in understanding the human lissencephalies and related disorders. LIS1 heterozygous loss-of-function deletions and point mutations, as well as Doublecortin mutations in males, lead to a very similar phenotype, termed type 1 lissencephaly. Additionally, Doublecortin mutations in females lead to a more variable subcortical band heterotopia. Given the similarities between the lissencephaly phenotypes that result from aberrations in these genes, it is important to review the genetics of these disorders. In order to begin to understand the cell biology of the LIS1 protein and the Doublecortin protein, potentially interacting pathways need to be emphasized. Another human genetic disorder with an interestingly similar phenotype has a mouse correlate that has been well characterized. This surprising finding may lead to further understanding of LIS1 protein and of Doublecortin protein. Furthermore, mouse modeling of the aforementioned human disorders now holds promise for enabling us finally to understand the formation of the most complex organ that nature has produced - the human brain.
AbstractThe incidence of mutations in the X-linked gene doublecortin in patients with “double cortex” syndrome (DC; also called subcortical band heterotopia or laminar heterotopia) and familial DC with lissencephaly was investigated in a cohort of 8 pedigrees and 47 sporadic patients with DC examined at the Division of Neurogenics, Beth Israel Deaconess Medical Center, Boston, and multiple centers in the US and abroad.
Galter Health Sciences Library, Northwestern University · 1999 · 0 citations · open access
Double Cortex Syndrome
AbstractThe incidence of mutations in the X-linked gene doublecortin in patients with double cortex syndrome (DC; also called subcortical band heterotopia or laminar heterotopia) and familial DC with lissencephaly was investigated in a cohort of 8 pedigrees and 47 sporadic patients with DC examined at the Division of Neurogenics, Beth Israel Deaconess Medical Center, Boston, and multiple centers in the US and abroad.
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.
