DeCure for Syndromic X-linked intellectual disability 34
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for syndromic X-linked intellectual disability 34 — 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 moduleSyndromic X-linked intellectual disability 34 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 syndromic x-linked intellectual disability 34 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
non-POU domain containing octamer binding (NONO) — NONO 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 3SDE · 1.9 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Syndromic X-linked intellectual disability 34 is not mentioned in any of the provided abstracts. The abstracts discuss X-linked intellectual disability broadly, fragile X syndrome, and a specific NLGN4X mutation in non-syndromic XLID, but none of them name or describe syndromic X-linked intellectual disability 34 as a distinct entity.
One abstract from 2020 notes that more than 141 genes on the X chromosome have been linked to XLID since 1991, and that the classical division into syndromic and non-syndromic forms is not always clear-cut because different variants in the same gene can produce either phenotype. A 2015 report describes two brothers with non-syndromic XLID carrying a novel NLGN4X splicing mutation (g.1202C>A), identified by X exome sequencing and confirmed by Sanger sequencing. The mother was heterozygous with a completely skewed X inactivation pattern and was unaffected. The mutation was absent in an unaffected daughter.
A 2017 study used a fly model of fragile X syndrome to screen drugs, finding that inhibitors of LIMK1 reduced hyperactive locomotion in flies and also reduced hyperactivity in a mouse model. A 2011 review states that fragile X syndrome is the most common inherited form of intellectual disability and that pharmaceutical therapies targeting it might become a benchmark for CNS drug discovery, but it provides no specific drug results.
No clinical trial data, survival figures, or response rates for any drug are reported in these abstracts. What is missing for syndromic X-linked intellectual disability 34 specifically is any mention of the gene or mutation involved, any animal model, any drug screen, and any clinical or preclinical treatment data. Without that basic molecular and phenotypic characterisation, no drug development or trial design can begin.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Investigation · 2012 · 329 citations · open access
Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
AbstractFragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and is also linked to other neurologic and psychiatric disorders. FXS is caused by a triplet expansion that inhibits expression of the FMR1 gene; the gene product, FMRP, regulates mRNA metabolism in the brain and thus controls the expression of key molecules involved in receptor signaling and spine morphology. While there is no definitive cure for FXS, the understanding of FMRP function has paved the way for rational treatment designs that could potentially reverse many of the neurobiological changes observed in FXS. Additionally, behavioral, pharmacological, and cognitive interventions can raise the quality of life for both patients and their families.
Non‐syndromic X linked intellectual disability: Current knowledge in light of the recent advances in molecular and functional studies
AbstractSince the discovery of the FMR1 gene and the clinical and molecular characterization of Fragile X Syndrome in 1991, more than 141 genes have been identified in the X-chromosome in these 28 years thanks to applying continuously evolving molecular techniques to X-linked intellectual disability (XLID) families. In the past decade, array comparative genomic hybridization and next generation sequencing technologies have accelerated gene discovery exponentially. Classically, XLID has been subdivided in syndromic intellectual disability (S-XLID)-where intellectual disability (ID) is always associated with other recognizable physical and/or neurological features-and non-specific or non-syndromic intellectual disability (NS-XLID) where the only common feature is ID. Nevertheless, new advances on the study of these entities have showed that this classification is not always clear-cut because distinct variants in several of these XLID genes can result in S-XLID as well as in NS-XLID. This review focuses on the current knowledge on the XLID genes involved in non-syndromic forms, with the emphasis on their pathogenic mechanism, thus allowing the possibility to elucidate why some of them can give both syndromic and non-syndromic phenotypes.
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.
AbstractDrug Development
The intellectual disability called fragile X syndrome is associated with abnormal synaptic morphology. Kashima et al. performed a high-throughput drug screen that used the hyperactive locomotion of a fly model of this disease as a behavioral marker. Inhibitors of LIMK1, a kinase involved in the pathogenesis of the disease, ameliorated the neurological and behavioral phenotypes in the fly model and also reduced hyperactivity in a mouse disease model. This method may aid in future drug development for fragile X syndrome, for which there are few treatment options at present.
Sci. Signal. 10 , eaai8133 (2017).
Greater South Information System · 2015 · 0 citations · open access
Non-Syndromic X Linked Intellectual Disability in Two Brothers with A Novel NLGN4X Gene Splicing Mutation (NC_018934.2: g. 1202C>A)
AbstractX-linked Intellectual Disability (XLID) is an extremely heterogeneous disorder for which many of the causative genes are still unknown.So far, more than one hundred genes of the X chromosome have been found to be altered in males manifesting intellectual disability (ID).NLGN4X is an XLID gene, which has been found, involved in autism and Asperger syndrome involving causative coding mutations.Up to now a few pathological mutations in the promoter and the 5' UTR have been identified.Here we report a non-syndromic X linked Intellectual disability in two brothers with a novel NLGN4X splicing mutation predicted to have a pathogenic effect by the activation of an exonic cryptic acceptor site, with presence of one or more cryptic branch point(s).This mutation g.1202C>A (Genbank accession number NC_018934.2) was identified through X exome sequencing.It was confirmed by Sanger sequencing.The mother was heterozygous with a skewed X inactivation pattern (100%).She is not affected.This variant was predicted to change the splicing process leading to potential alteration of the mRNA.This mutation segregates with the pathological phenotype in all the affected males.However, it was absent in the non-affected daughter, we suggest that it could be in favor of genotype-phenotype correlation.This study also confirms the efficiency of X exome sequencing for identifying specific genetic conditions not clinically suspected.
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.
