DeCure for Severe X-linked intellectual disability, Gustavson type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for severe X-linked intellectual disability, Gustavson 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 moduleSevere X-linked intellectual disability, Gustavson 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 severe x-linked intellectual disability, gustavson 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.
What the evidence adds up to
No abstract in this set describes a treatment, drug, or clinical trial for severe X-linked intellectual disability, Gustavson type. The 2013 review states that X-linked intellectual disability affects 1% to 3% of the population and that 102 XLID genes had been identified at that time. It discusses the molecular roles of several XLID proteins in synapse structure and function, but provides no patient data, survival figures, or response rates.
The 2022 update reports that 21 new XLID genes were identified between 2017 and 2022, bringing the total number of named XLID syndromes to 199, of which 42 (21%) remain unresolved at the molecular level. Among 108 numbered nonsyndromic XLID families, 27 (25%) also lack a molecular diagnosis. The pace of gene discovery has slowed, but the density of XLID genes on the X chromosome remains twice that of intellectual disability genes on autosomes. No treatment outcomes are reported.
The second 2022 review covers X-linked copy number variants (CNVs) and discusses the modifying effect of X-chromosome inactivation on phenotype. It notes problems in interpreting the clinical significance of X-linked CNVs. Again, no drug, no trial, no survival or response data appear.
What is missing is any clinical trial, any tested drug, any patient survival or response data, and any funding for treatment studies in this specific condition. The abstracts show that the molecular causes are still being catalogued, and that for many XLID syndromes the gene itself remains unknown. Without a resolved molecular target, no rational drug-repurposing trial can be designed, and no patient stratification strategy exists.
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.
AbstractGenes that are involved in the transcription process, mitochondrial function, glycoprotein metabolism, and ubiquitination dominate the list of 21 new genes associated with X-linked intellectual disability since the last update in 2017. The new genes were identified by sequencing of candidate genes (2), the entire X-chromosome (2), the whole exome (15), or the whole genome (2). With these additions, 42 (21%) of the 199 named XLID syndromes and 27 (25%) of the 108 numbered nonsyndromic XLID families remain to be resolved at the molecular level. Although the pace of discovery of new XLID genes has slowed during the past 5 years, the density of genes on the X chromosome that cause intellectual disability still appears to be twice the density of intellectual disability genes on the autosomes.
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.
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.
