DeCure for Syndromic X-linked intellectual disability Nascimento type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for syndromic X-linked intellectual disability Nascimento 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 Nascimento 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 nascimento 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
ubiquitin conjugating enzyme E2 A (UBE2A) — UBE2A 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 6CYO · 1.85 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
No clinical trial or treatment study for syndromic X-linked intellectual disability Nascimento type was found in the provided abstracts. The abstracts are reviews of X-linked intellectual disability (XLID) genetics and neurobiology, not reports of drug testing. XLID affects 1% to 3% of the population, with a prevalence of 2.6 cases per 1,000, and accounts for over 10% of all intellectual disability cases. Over 141 XLID genes have been identified, and mutations in about 10% of X-chromosome genes are implicated in roughly 50% of families. Two thirds of XLID cases are thought to be non-syndromic. The abstracts describe the ARX gene, which is responsible for about 9.5% of XLID cases and is highly conserved, with mutations predicted to be highly pathogenic. The abstracts note that XLID classification into syndromic and non-syndromic forms is not always clear-cut, as distinct variants in several genes can produce both phenotypes.
The abstracts discuss molecular mechanisms, including the role of XLID proteins in synapse structure and function, cell migration, and neural network formation. The ARX gene is described as having a role in the Wnt/β-catenin signalling pathway, and its deficiency is said to cause irreversible defects mainly in the brain. Fragile X syndrome is noted as the most frequent and most studied XLID syndrome. The abstracts state that it is now possible to identify 64% of the genetic defects in XLID families with obligate female carriers. No concrete numbers on survival, response rates, or sample sizes from any interventional study are provided, because none are reported.
What is still missing for any potential drug repurposing in syndromic X-linked intellectual disability Nascimento type is any clinical trial data whatsoever. The abstracts provide no evidence of a tested drug, no patient stratification strategy, and no funded trial design. The research remains at the level of gene discovery and mechanistic review, with no translational step into a treatment study.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Neuroscientist · 2013 · 51 citations
The Neurobiology of X-Linked Intellectual Disability
AbstractX-linked intellectual disability (XLID) affects 1% to 3% of the population. XLID subsumes several heterogeneous conditions, all of which are marked by cognitive impairment and reduced adaptive skills. XLID arises from mutations on the X chromosome; to date, 102 XLID genes have been identified. The proteins encoded by XLID genes are involved in higher brain functions, such as cognition, learning and memory, and their molecular role is the subject of intense investigation. Here, we review recent findings concerning a representative group of XLID proteins: the fragile X mental retardation protein; methyl-CpG-binding protein 2 and cyclin-dependent kinase-like 5 proteins, which are involved in Rett syndrome; the intracellular signaling molecules of the Rho guanosine triphosphatases family; and the class of cell adhesion molecules. We discuss how XLID gene mutations affect the structure and function of synapses.
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.
Encyclopedia of Life Sciences · 2017 · 0 citations
Genetics of <scp>X</scp> ‐Linked Intellectual Disability
AbstractAbstract X‐linked intellectual disability (XLID), formerly called mental retardation , refers to a group of inherited disorders characterised by varying degrees of intellectual disability caused by mutations in various genes present on the X‐chromosome. Deleterious mutations in ∼ 10% of X‐chromosome X genes are implicated in causing XLID disorders in ∼ 50% of families. The remaining XLID genes are expected to be rare and even private to individual families. Historically, XLID is divided into syndromic (IDXS) and nonsyndromic (IDX). At least 209 different XLID disorders have been described including 143 forms of syndromic mental retardation. Fragile X syndrome is the most frequent syndrome and most studied XLID syndrome. It is now possible to identify 64% of the genetic defects in XLID families with obligate female carriers. Most of the mutated genes in XLID are thought to influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain. Thus, the diagnosis of intellectual disability in a child has an enormous impact in most affected families. Genetic counselling is strongly recommended to family members. Key Concepts X‐linked intellectual disability (XLID) is a very heterogeneous set of conditions responsible for a large proportion of inherited mental retardation. XLID can be divided into syndromic (MRID) and nonsyndromic (IDX). Genes involved in XLID influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in the brain. Intellectual disability phenotype can emerge as the final common pathway for many different types of abnormal cellular processing. Genetic counselling is an important part in general management in the case of intellectual disability.
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.
