DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for non-syndromic intellectual disability — screening already-approved drugs against its 5-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 intellectual disability maps to a 5-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 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
sodium voltage-gated channel alpha subunit 2 (SCN2A) — SCN2A 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 3beta,14beta,17beta,25rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6J8E · 3.0 Å · ligand (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en (9Z9). Experimental structure, not a prediction.
What the evidence adds up to
No drug treatment has been tested in a controlled trial for non-syndromic intellectual disability (NS-ID) in the abstracts provided. A 2009 review raised the possibility that targeted drug treatments might be developed to enhance learning, based on identified molecular mechanisms in specific intellectual disability syndromes, but it did not report any clinical results. A 2017 gene-network analysis of 245 candidate NS-ID genes found over-representation in axon guidance, synaptogenesis, cell adhesion and neurotransmission pathways, and noted enrichment of dopaminergic and glutamatergic pathways among genes shared with syndromic intellectual disability and related neuropsychiatric disorders. That study suggested modulation of these neurotransmitter systems as a potential contributor to synaptic dysfunction, but offered no efficacy data.
Outcome measurement remains a recognised problem. A 2020 review stated that tools assessing intellectual and adaptive functioning have rarely been used as primary outcome measures in treatment trials for core symptoms of intellectual disability, and that further study is needed on their usefulness for measuring change. The review proposed solutions including out-of-age-range testing, alternative metrics, and development of new measures, but no such validated measure for NS-ID drug trials is described in these abstracts.
One 2021 study of 169 patients in a specialist intellectual disability inpatient unit reported that Health of the Nation Outcome Scales for people with learning disabilities (HoNOS-LD) scores decreased significantly from admission to discharge for all patient categories. That study did not involve any drug treatment; it assessed outcomes of inpatient care and recommended HoNOS-LD for demonstrating treatment effectiveness in that setting. No data on drug repurposing, response rates, or survival are present in any of the abstracts.
What is missing is any completed or ongoing clinical trial of a drug for NS-ID, any validated outcome measure specific to drug trials in this population, and any evidence that the genetic pathways identified can be translated into a safe and effective treatment. Funding for such trials, a trial design that can account for the genetic heterogeneity of NS-ID, and patient stratification by genetic subtype are all absent from the current literature.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal on Intellectual and Developmental Disabilities · 2020 · 35 citations
Outcome Measures for Core Symptoms of Intellectual Disability: State of the Field
AbstractIntellectual disability (ID) is defined by impairments in intellectual and adaptive functioning. As such, tools designed to assess these domains would theoretically be ideal outcome measures for treatment trials targeting core symptoms of ID. However, measures of intellectual and adaptive functioning have rarely been used as primary outcome measures to date and further study is needed regarding their usefulness to measure change. This area of inquiry is important because promising, mechanism-modifying treatments for conditions leading to ID are being initiated. To show efficacy, these treatments need to demonstrate an impact on core features of ID. After reviewing literature on this topic, we suggest solutions to several problems outlined, including use of out-of-age-range testing, alternative metrics, and development of new measures.
Journal of Applied Research in Intellectual Disabilities · 2021 · 16 citations · open access
An 8‐year study of admissions and discharges to a specialist intellectual disability inpatient unit
AbstractBACKGROUND: In the United Kingdom, policy change has led to specialist intellectual disability inpatient bed reduction. Little evidence exists assessing the results for patients admitted to such units. This study evaluates the outcomes of a specialist intellectual disability inpatient unit. METHOD: Gender/age/ethnicity/intellectual disability severity/co-morbid psychiatric/developmental disorders, treatment length and stay data were collected. The health of the nation outcome scales for people with learning disabilities (HoNOS-LD) scores at admission, treatment completion and discharge were recorded. Analysis of these multiple variables and correlations within different patient groups was investigated using various statistical tests. RESULTS: Of 169/176 patients (2010-2018), admission to discharge, HoNOS-LD global and all individual items score decreased significantly, for all patient categories. Treatment completion to discharge duration was significant for the whole cohort. CONCLUSIONS: This is the largest study of intellectual disability inpatient outcomes. Discharge from the hospital appears not associated with duration of treatment. Using HoNOS-LD to demonstrate treatment effectiveness is recommended.
Journal of Neurogenetics · 2017 · 15 citations · open access
Gene networks associated with non-syndromic intellectual disability
AbstractNon-syndromic intellectual disability (NS-ID) is a genetically heterogeneous disorder, with more than 200 candidate genes to date. Despite the increasing number of novel mutations detected, a relatively low number of recurrently mutated genes have been identified, highlighting the complex genetic architecture of the disorder. A systematic search of PubMed and Medline identified 245 genes harbouring non-synonymous variants, insertions or deletions, which were identified as candidate NS-ID genes from case reports or from linkage or pedigree analyses. From this list, 33 genes are common to syndromic intellectual disability (S-ID) and 58 genes are common to certain neurological and neuropsychiatric disorders that often include intellectual disability as a clinical feature. We examined the evolutionary constraint and brain expression of these gene sets, and we performed gene network and protein–protein interaction analyses using GeneGO MetaCoreTM and DAPPLE, respectively. The 245 NS-ID candidate genes were over-represented in axon guidance, synaptogenesis, cell adhesion and neurotransmission pathways, all of which are key neurodevelopmental processes for the establishment of mature neuronal circuitry in the brain. These 245 genes exhibit significantly elevated expression in human brain and are evolutionarily constrained, consistent with expectations for a brain disorder such as NS-ID that is associated with reduced fecundity. In addition, we report enrichment of dopaminergic and glutamatergic pathways for those candidate NS-ID genes that are common to S-ID and/or neurological and neuropsychiatric disorders that exhibit intellectual disability. Collectively, this study provides an overview and analysis of gene networks associated with NS-ID and suggests modulation of neurotransmission, particularly dopaminergic and glutamatergic systems as key contributors to synaptic dysfunction in NS-ID.
Australian & New Zealand Journal of Psychiatry · 2009 · 8 citations
Can Drug Treatments Enhance Learning in Subjects with Intellectual Disability?
AbstractRecent research has identified specific molecular mechanisms that might account for impaired learning in particular intellectual disability syndromes. These and other findings raise the possibility that targeted drug treatments might be developed to enhance learning in subjects with intellectual disability. This review considers strategies for developing treatments, and identifies critical issues that will need to be considered in such programmes.
Gene networks associated with non-syndromic intellectual disability
AbstractNon-syndromic intellectual disability (NS-ID) is a genetically heterogeneous disorder, with more than 200 candidate genes to date. Despite the increasing number of novel mutations detected, a relatively low number of recurrently mutated genes have been identified, highlighting the complex genetic architecture of the disorder. A systematic search of PubMed and Medline identified 245 genes harbouring non-synonymous variants, insertions or deletions, which were identified as candidate NS-ID genes from case reports or from linkage or pedigree analyses. From this list, 33 genes are common to syndromic intellectual disability (S-ID) and 58 genes are common to certain neurological and neuropsychiatric disorders that often include intellectual disability as a clinical feature. We examined the evolutionary constraint and brain expression of these gene sets, and we performed gene network and protein–protein interaction analyses using GeneGO MetaCore<sup>TM</sup> and DAPPLE, respectively. The 245 NS-ID candidate genes were over-represented in axon guidance, synaptogenesis, cell adhesion and neurotransmission pathways, all of which are key neurodevelopmental processes for the establishment of mature neuronal circuitry in the brain. These 245 genes exhibit significantly elevated expression in human brain and are evolutionarily constrained, consistent with expectations for a brain disorder such as NS-ID that is associated with reduced fecundity. In addition, we report enrichment of dopaminergic and glutamatergic pathways for those candidate NS-ID genes that are common to S-ID and/or neurological and neuropsychiatric disorders that exhibit intellectual disability. Collectively, this study provides an overview and analysis of gene networks associated with NS-ID and suggests modulation of neurotransmission, particularly dopaminergic and glutamatergic systems as key contributors to synaptic dysfunction in NS-ID.
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.
