DeCure for Non-syndromic X-linked intellectual disability
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for non-syndromic X-linked intellectual disability — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNon-syndromic X-linked intellectual disability maps to a 31-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 non-syndromic x-linked intellectual disability 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
FERM and PDZ domain containing 4 (FRMPD4) — FRMPD4 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4WND · 1.5 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
The 2011 review on fragile X syndrome, a syndromic form of X-linked intellectual disability, describes a genetic condition caused by a full mutation in the FMR1 gene. It notes that premutation carriers are prone to fragile X tremor-ataxia syndrome in mid-life and that women with premutations experience premature ovarian insufficiency. The review mentions that imbalances in GABA-glutamate mediated postsynaptic pathways are a current focus of psychopharmacological research, but states that results of syndrome-specific medication trials are awaited. A separate 2011 article frames fragile X syndrome as a potential benchmark for CNS drug discovery, but provides no trial data.
The 2015 report describes two brothers with non-syndromic X-linked intellectual disability caused by a novel NLGN4X gene splicing mutation, g.1202C>A. The mutation was identified through X exome sequencing and confirmed by Sanger sequencing. The mother was heterozygous with a skewed X inactivation pattern (100%) and was not affected. The mutation was absent in a non-affected daughter. The authors suggest this supports a genotype-phenotype correlation and confirm the efficiency of X exome sequencing for identifying specific genetic conditions not clinically suspected. No treatment or intervention is discussed in this report.
No drug, compound, or intervention is tested in any of these abstracts. The 2011 reviews mention that syndrome-specific medication trials are awaited, but provide no results. The 2015 case report is purely genetic. What is missing for non-syndromic X-linked intellectual disability specifically is any clinical trial data, any proposed molecular target for drug repurposing, and any patient stratification beyond the single family described. Funding for preclinical models of NLGN4X mutations and for trials that might test existing compounds against this target is absent.
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 Psychiatry · 2011 · 33 citations
Fragile X syndrome
AbstractPURPOSE OF REVIEW: Advances in developmental neuropsychiatry and the mental health needs of people with intellectual disability are creating ever greater understanding of the critical associations between human genome variations and psychological functioning throughout lifespan and across the entire intellectual ability spectrum. This review highlights the recent developments and their clinical implications for people with fragile X syndrome. RECENT FINDINGS: There is substantial evidence for individuals of all ages and intellectual abilities being prone to psychological profiles determined not only by having a fragile X gene full mutation, but also by having premutations and intermediate alleles. The importance of these genetic contributors to mental life, if anything, increases with age. Premutation carriers are prone to neurodegenerative mid-life fragile X tremor-ataxia syndrome. Women with premutations experience premature ovarian insufficiency. Imbalances in the (gamma amino butyrie acid)-glutamate mediated postsynaptic cascade central neuronal pathways are a current focus of psychopharmacological enquiry, giving the hope of syndrome-specific medical treatments. SUMMARY: Findings from genetic, neurological, biochemical, psychological and pharmacological research are combining to revolutionize understanding of the pathogenesis of developmental and psychological disabilities affecting individuals with fragile X syndrome irrespective of age, intelligence level and gene mutation status. Results of syndrome-specific medication trials are awaited.
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.
X-Linked CNV in Pathogenetics of Intellectual Disability
AbstractThe review considers monogenic and chromosomal mutations associated with X-linked intellectual disability. Peculiarities of the development of the clinical phenotype in cases of different mutations were described. Special attention is paid to X-linked CNVs (microdeletions and microduplications). Chromosomal microaberrations most frequently found in patients with intellectual disability are presented. A modifying effect of X chromosome inactivation on the phenotype of carriers of X-linked mutations is discussed. The problems of interpretation of the clinical significance of X-linked CNVs are considered.
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.
