DeCure for Syndromic X-linked intellectual disability Siderius type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for syndromic X-linked intellectual disability Siderius 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 moduleSyndromic X-linked intellectual disability Siderius 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 syndromic x-linked intellectual disability siderius 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
PHD finger protein 8 (PHF8) — PHF8 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 iidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3KV4 · 2.19 Å · ligand FE (II) ION (FE2). Experimental structure, not a prediction.
What the evidence adds up to
Three brothers with a novel missense mutation in MED12 (c.5922G>T, p.Glu1974His) were reported in 2015 as having non-syndromic X-linked intellectual disability. Only seven pathological MED12 mutations had been identified at that time. The authors suggested the mutation might support genotype-phenotype correlations.
X-linked intellectual disability has a prevalence of 2.6 per 1,000 in the general population and accounts for over 10% of all intellectual disability cases. Two thirds of XLID cases are thought to be non-syndromic. More than 141 genes on the X-chromosome have been linked to XLID since 1991. The classification into syndromic and non-syndromic forms is not clear-cut, because distinct variants in several XLID genes can produce both syndromic and non-syndromic phenotypes.
The ARX gene is one of the most frequently mutated XLID genes, after FMR1 and MECP2. ARX mutations are responsible for about 9.5% of XLID cases. More than 110 mutations in ARX have been reported. The phenotype always involves intellectual disability and often includes epilepsy, infantile spasms, hand dystonia, lissencephaly, autism, or dysarthria. Bioinformatics analysis of ARX shows it is a highly conserved protein with a role in the Wnt/β-catenin signalling pathway, and its deficiency is predicted to cause irreversible brain defects.
No clinical trial data, no drug intervention, and no treatment effect are reported in any of these abstracts. What is missing is any trial design, any patient stratification strategy, and any funding for a drug-repurposing study in this specific genetic condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Case Reports · 2015 · 56 citations · open access
Nonsyndromic X‐linked intellectual deficiency in three brothers with a novel <i><scp>MED</scp>12</i> missense mutation [c.5922G>T (p.Glu1974His)]
AbstractX-linked intellectual deficiency (XLID) is a large group of genetic disorders. MED12 gene causes syndromic and nonsyndromic forms of XLID. Only seven pathological mutations have been identified in this gene. Here, we report a novel mutation segregating with XLID phenotype. This mutation could be in favor of genotype-phenotype correlations.
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.
Journal of genetics and molecular biology · 2019 · 4 citations
ARX gene with an impressive role in X-linked intellectual disability
AbstractIntellectual disability is the most common neurodevelopmental defect in the worldwide. X-linked intellectual disability (XLID) is the frequent form of intellectual disability which includes a heterogeneous group of inherited disorders emerging as various degrees of intellectual disabilities. XLID has a prevalence of 2.6 cases per 1,000 in the general population and accounts for over 10% of all cases of intellectual disability. Based on associated phenotypes, XLID is subdivided into syndromic (S-XLID) and non-syndromic (NS-XLID) forms; where two third of XLID cases are thought to be non-syndromic. Among the non-syndromic form, the aristalessrelated homeobox gene (ARX) gene is one of the ideal candidates to be evaluated in NS-XLID, since its mutations are responsible for about 9.5% of XLID cases. The ARX is located on the Xp22.13 genomic region and encodes a highly conserved protein with a considerable role in Wnt/β-catenin signaling pathway. Base on review literature, mutations in ARX gene has a particular influence on the critical processes associated with the brain development. Our results in bioinformatics study of molecular features, second and quaternary structures of ARX gene and also the phylogeny tree of ARX protein is showed that the ARX is a highly conserved protein with a substantial role in an important developmental pathway and its deficiency can cause irreversible defects, mainly in brain, that leads to the development of XLID as a common form of intellectual disability and also, the sequence alignment of this protein with other spices confirms that the functional domains of ARX protein are highly conserved, thus it has been predicted that the mutations of this gene is highly pathogenic. Alongside, we mainly focused to gather the data addressing the structural properties of ARX protein and bioinformatics assay of this protein to find the important role of ARX gene in the integrity of normal brain development.
Oxford University Press eBooks · 2016 · 3 citations
Developmental Abnormalities Due to Mutations in the Aristaless-Related Homeobox Gene
AbstractAbstract Intellectual disability is a broad spectrum of neurodevelopmental disorders of the brain that combined affect approximately one in 50 individuals worldwide. X-linked intellectual disabilities represent a group of disorders where mutations arise on the X-chromosome. XLID is clinically complex and genetically heterogeneous. In excess of 100 genes are currently known. One of the most frequently mutated XLID genes (after e.g. FMR1 or MECP2) is the Aristaless related homeobox (ARX) gene. More than 110 mutations have been reported in ARX. The phenotype always involves intellectual disability and often also epilepsy, infantile spasms, hand dystonia, lissencephaly, autism or dysarthria. This chapter summarizes currently known mutations in ARX and their clinical manifestations and explores what is known about the underlying molecular and cellular mechanisms.
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.
