DeCure for Intellectual disability-hypotonic facies syndrome, X-linked, 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability-hypotonic facies syndrome, X-linked, 1 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIntellectual disability-hypotonic facies syndrome, X-linked, 1 maps to a 2-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 intellectual disability-hypotonic facies syndrome, x-linked, 1 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
ATRX chromatin remodeler (ATRX) — ATRX 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9L06 · 3.4 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
The 2015 abstract describes fragile X syndrome as a sex-linked intellectual disability caused by an expanded CGG trinucleotide repeat in the FMR1 gene, leading to epigenetic silencing of the FMRP protein. It does not report any drug intervention or clinical trial. The 2022 abstract reports exome sequencing in a 15-year-old boy with primary microcephaly and intellectual disability, identifying a previously reported missense variant in the ATRX gene (c.5182G>C, p.Ala1728Pro) that segregated with the new clinical feature of primary microcephaly in the pedigree. The variant was classified as likely pathogenic according to ACMG guidelines. No treatment, drug, or outcome data are provided. The 2016 abstract summarises mutations in the ARX gene, which is one of the most frequently mutated X-linked intellectual disability genes after FMR1 and MECP2. Over 110 mutations in ARX have been reported, and the phenotype always involves intellectual disability, often with epilepsy, infantile spasms, hand dystonia, lissencephaly, autism, or dysarthria. No drug, trial, or survival data are given.
None of the three abstracts describe any drug treatment, repurposed or otherwise, for intellectual disability-hypotonic facies syndrome, X-linked, 1. No response rates, survival figures, or sample sizes for any intervention appear in these texts. The 2022 abstract adds one new clinical observation (primary microcephaly) to the known phenotype of ATRX mutations, but offers no therapeutic data. The 2015 and 2016 abstracts are reviews of genetic and epigenetic mechanisms, not clinical studies.
What is missing is any clinical trial testing a drug in patients with this specific syndrome, any funding for such a trial, and any patient stratification strategy that might identify which genetic variants respond to which agents. Without these, the abstracts provide only genetic diagnosis, not treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2015 · 3 citations
Epigenetic diagnostics for neuropsychiatric disorders
AbstractMartin and Bell's1 1943 report of a pedigree with a sex-linked form of intellectual disability described what is now referred to as fragile X syndrome (FXS), caused by an expanded (>200) CGG trinucleotide repeat within the 5′ untranslated region of the fragile X mental retardation 1 ( FMR1 ) gene. This results in epigenetic silencing of the encoded fragile X mental retardation protein (FMRP).1,2 The term epigenetic refers to chemical modifications of DNA and associated chromatin proteins that alter activity states of the genome without requiring heritable changes to DNA itself.3 Studies of inherited neuropsychiatric disorders have contributed greatly to our understanding of the molecular basis of human cognition, mood, and behavior; the field of neuroepigenetics continues to expand and gain importance.4
Molecular Genetics & Genomic Medicine · 2022 · 3 citations · open access
X‐linked mental retardation‐hypotonic facies syndrome: Exome sequencing identifies novel clinical characteristics associated with c.5182G>C mutation in the <i>ATRX</i> gene
AbstractBACKGROUND: X-linked mental retardation-hypotonic facies syndrome-1 (MRXFH1), caused by a mutation in the ATRX gene, is a rare syndromic form of X-linked mental retardation (XLMR) that is mainly characterized by severe intellectual disability, dysmorphic facies, and skewed X-inactivation pattern in carrier women. METHOD: In this study, due to the genetic heterogeneity of the disease, we performed exome sequencing (ES) on a 15-year-old boy with primary microcephaly and intellectual disability. Also, Sanger sequencing, cosegregation analysis, and structural modeling were done to identify and verify the causative variant in the proband and other affected individuals in the family. In addition, we collected data from previously reported cases to compare with our patients' phenotypes. RESULTS: ES revealed a previously reported missense variant in the ATRX gene (c.5182G > C, p.Ala1728Pro), segregating with the new clinical characteristic including primary microcephaly in the pedigree. This variant meets the criteria of being likely pathogenic based on the ACMG variant interpretation guideline. CONCLUSIONS: The findings of this study extend the spectrum of phenotypes associated with the identified variant and provide further details on its clinical features.
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.
