DeCure for X-linked intellectual disability, van Esch type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for X-linked intellectual disability, van Esch 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 moduleX-linked intellectual disability, van Esch 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 x-linked intellectual disability, van esch 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
DNA polymerase alpha 1, catalytic subunit (POLA1) — POLA1 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8QJ7 · 3.07 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
X-linked intellectual disability, van Esch type, is one of a heterogeneous group of conditions caused by mutations on the X chromosome. The broader category of X-linked intellectual disability affects 1% to 3% of the population, and 102 XLID genes have been identified as of 2013. The proteins these genes encode are involved in higher brain functions such as cognition, learning, and memory, and mutations affect the structure and function of synapses. No specific drug or treatment is mentioned in any of the abstracts.
One 2009 study found no evidence for a higher incidence of recent positive selection on X-linked intellectual disability genes compared to autosomal ones, or compared to control genes. However, X-linked genes subject to recent positive selection were concentrated in the Rho GTP-ase pathway, a key signalling pathway in neural development. Among all intellectual disability genes, there was evidence for a higher incidence of recent positive selection on genes involved in DNA repair, but not for genes involved in other functions. A 2001 review noted that a large proportion of mental retardation is genetically determined and can be molecularly defined and precisely diagnosed, but it also discussed limitations affecting diagnosis and the need for new approaches.
No clinical trial data, no survival or response rates, and no drug names appear in these abstracts. The 2001 review states that building knowledge about molecular processes will bring benefits to patient management, disease prevention, and ultimately disease treatment, but it does not describe any existing treatment. What is still missing is any clinical trial testing a drug for van Esch type specifically, any patient stratification based on the specific gene mutation, and the funding to move from genetic characterisation to therapeutic development.
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.
Evolutionary Applications · 2009 · 11 citations · open access
Evolutionary genomics of human intellectual disability
AbstractPrevious studies have postulated that X-linked and autosomal genes underlying human intellectual disability may have also mediated the evolution of human cognition. We have conducted the first comprehensive assessment of the extent and patterns of positive Darwinian selection on intellectual disability genes in humans. We report three main findings. First, as noted in some previous reports, intellectual disability genes with primary functions in the central nervous system exhibit a significant concentration to the X chromosome. Second, there was no evidence for a higher incidence of recent positive selection on X-linked than autosomal intellectual disability genes, nor was there a higher incidence of selection on such genes overall, compared to sets of control genes. However, the X-linked intellectual disability genes inferred to be subject to recent positive selection were concentrated in the Rho GTP-ase pathway, a key signaling pathway in neural development and function. Third, among all intellectual disability genes, there was evidence for a higher incidence of recent positive selection on genes involved in DNA repair, but not for genes involved in other functions. These results provide evidence that alterations to genes in the Rho GTP-ase and DNA-repair pathways may play especially-important roles in the evolution of human cognition and vulnerability to genetically-based intellectual disability.
Expert Review of Molecular Diagnostics · 2001 · 2 citations
Molecular genetics of X-linked mental retardation: a complex picture emerging
AbstractMental retardation or intellectual disability is a heterogeneous group of disorders of the human brain affecting 2-3% of the general population. It is becoming evident that a large proportion of mental retardation is genetically determined, which means that it can be molecularly defined and thus precisely diagnosed. Building knowledge and understanding about molecular processes leading to 'malfunction of human brain' will clearly bring benefits to patient management, disease prevention and ultimately disease treatment and will also assist in tackling much harder questions of the molecular basis of human cognitive ability. In this review the current knowledge of the molecular genetics of X-chromosome-linked mental retardation and its nonspecific forms in particular is discussed, together with limitations affecting diagnosis and likely new approaches that need to be implemented.
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.
