DeCure for X-linked intellectual disability, Cabezas type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for X-linked intellectual disability, Cabezas type — 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 moduleX-linked intellectual disability, Cabezas type 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 x-linked intellectual disability, cabezas type 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
cullin 4B (CUL4B) — CUL4B 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4A0C · 3.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The 2011 review on fragile X syndrome states that intellectual disability was long considered immutable and that current medical practice aims only at symptom relief, not at altering underlying cognitive deficits. It raises the possibility that pharmaceutical therapies might one day treat the condition, but it offers no data on any specific drug or outcome. No drug is named, no trial is described, and no efficacy is claimed.
A 2017 case report describes a 5-year-old boy with severe intellectual disability who was diagnosed with Cabezas syndrome only after targeted exome sequencing found a novel nonsense mutation in the last coding exon of CUL4B. The report provides no treatment, no drug, and no follow-up data. It simply establishes the genetic diagnosis.
A 2018 study used long-read single molecule sequencing to examine tandem repeats on the X chromosome in three families with idiopathic X-linked intellectual disability. In male DNA samples, full repeat length sequences were obtained for 88–93% of targets and up to 99.6% of repeats with moderate GC content. In one family, a repeat expansion co-occurred with down-regulation of the neighbouring MIR222 gene, which has been linked to intellectual disability and to overexpression of FMR1 and NEFH. The study suggests tandem repeat mutations may be a hidden cause of X-linked intellectual disability, but it does not test any drug or intervention.
A 2016 article on molecular and genetic mechanisms of intellectual disability is a conference management advertisement and contains no scientific data whatsoever.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
ACS Chemical Neuroscience · 2011 · 19 citations · open access
Fragile X Syndrome: An Update on Developing Treatment Modalities
AbstractIntellectual disability (ID; mental retardation) is considered an immutable condition. Current medical practices are aimed at relieving symptoms and not at altering the underlying cognitive deficits. Scientific advancements from the past decade have led to the exciting possibility that ID may now be treatable. Moreover, pharmaceutical therapies targeting the most common form of inherited ID, Fragile X syndrome (FXS), may become the new benchmark for central nervous system (CNS) drug discovery: seeking cures for neurodevelopmental disorders.
Human Genome Variation · 2017 · 12 citations · open access
Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection
AbstractCabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B , thus diagnosing this patient with Cabezas syndrome.
BMC Medical Genomics · 2018 · 6 citations · open access
Mapping the landscape of tandem repeat variability by targeted long read single molecule sequencing in familial X-linked intellectual disability
AbstractBACKGROUND: The etiology of more than half of all patients with X-linked intellectual disability remains elusive, despite array-based comparative genomic hybridization, whole exome or genome sequencing. Since short read massive parallel sequencing approaches do not allow the detection of larger tandem repeat expansions, we hypothesized that such expansions could be a hidden cause of X-linked intellectual disability. METHODS: We selectively captured over 1800 tandem repeats on the X chromosome and characterized them by long read single molecule sequencing in 3 families with idiopathic X-linked intellectual disability. RESULTS: In male DNA samples, full tandem repeat length sequences were obtained for 88-93% of the targets and up to 99.6% of the repeats with a moderate guanine-cytosine content. Read length and analysis pipeline allow to detect cases of > 900 bp tandem repeat expansion. In one family, one repeat expansion co-occurs with down-regulation of the neighboring MIR222 gene. This gene has previously been implicated in intellectual disability and is apparently linked to FMR1 and NEFH overexpression associated with neurological disorders. CONCLUSIONS: This study demonstrates the power of single molecule sequencing to measure tandem repeat lengths and detect expansions, and suggests that tandem repeat mutations may be a hidden cause of X-linked intellectual disability.
Frontiers in Cellular Neuroscience · 2016 · 0 citations · open access
Molecular and genetic mechanisms of intellectual disability
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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.
