DeCure for Intellectual disability, autosomal dominant 48
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, autosomal dominant 48 — 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, autosomal dominant 48 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, autosomal dominant 48 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
Rac family small GTPase 1 (RAC1) — RAC1 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1I4D · 2.5 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
MED23 mutation p.R617Q was reported in 2011 to cosegregate with nonsyndromic autosomal recessive intellectual disability. The mutation impaired the response of JUN and FOS immediate early genes to serum mitogens by altering the interaction between enhancer-bound transcription factors and Mediator. Transcriptional dysregulation of these genes was also observed in cells from patients with other neurological disorders linked to mutations in other Mediator subunits or interacting proteins. No drug was tested in that study.
A 2025 study identified a homozygous c.1693T>C;p.(Tyr565His) variant in SLC6A17 in a Pakistani family with autosomal recessive intellectual disability, specifically mental retardation autosomal recessive 48 (MRT48), which is a recessive syndromic disorder characterised by progressive tremors, speech impairment, and behavioural problems. The variant segregated with the phenotype in the extended family. No treatment or drug was investigated.
The 2011 Fragile X syndrome update states that intellectual disability was long considered immutable and that current medical practices aim only at relieving symptoms, not altering cognitive deficits. It notes that pharmaceutical therapies targeting Fragile X syndrome might become a benchmark for CNS drug discovery, but no specific drug is reported as effective. A 2022 review of Bardet-Biedl syndrome mouse models states that there are limited pharmacological interventions for intellectual disability, partly due to poor understanding and heterogeneity, and that there are limited mouse models. A 2020 review of outcome measures for core symptoms of intellectual disability notes that measures of intellectual and adaptive functioning have rarely been used as primary outcome measures in treatment trials, and that further study is needed on their usefulness to measure change.
No drug has been tested in any clinical trial for MRT48. No animal model of the specific SLC6A17 or MED23 mutations described here has been used to test a pharmacological intervention. What is missing is any funded preclinical or clinical programme aimed at this specific genetic form of intellectual disability, any validated outcome measure sensitive to change in this population, and any patient stratification strategy that would allow a trial to detect a signal if a drug were available.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science · 2011 · 118 citations
<i>MED23</i> Mutation Links Intellectual Disability to Dysregulation of Immediate Early Gene Expression
AbstractMED23 is a subunit of the Mediator complex, a key regulator of protein-coding gene expression. Here, we report a missense mutation (p. R617Q) in MED23 that cosegregates with nonsyndromic autosomal recessive intellectual disability. This mutation specifically impaired the response of JUN and FOS immediate early genes (IEGs) to serum mitogens by altering the interaction between enhancer-bound transcription factors (TCF4 and ELK1, respectively) and Mediator. Transcriptional dysregulation of these genes was also observed in cells derived from patients presenting with other neurological disorders linked to mutations in other Mediator subunits or proteins interacting with MED. These findings highlight the crucial role of Mediator in brain development and functioning and suggest that altered IEG expression might be a common molecular hallmark of cognitive deficit.
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.
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.
Iowa Research Online (The University of Iowa) · 2022 · 0 citations · open access
Behavioral and brain phenotypes of mouse models of Bardet-Biedl Syndrome
AbstractIntellectual disability (ID) is one of the most common neurodevelopmental disorders, affecting 1% of the population globally. Clinically, ID is characterized by a deficit in intellectual functioning and adaptive functioning. There are limited pharmacological interventions for ID, partially due to a poor understanding of ID and the heterogeneous nature of ID In addition, there are limited mouse models of ID.
Biallelic Variant in <scp> <i>SLC6A17</i> </scp> in a Pakistani Family With Autosomal Recessive Intellectual Disability
AbstractAutosomal recessive intellectual disability affects 1%-3% of the general population and is a major concern in countries where consanguineous marriages are common. Mental retardation autosomal recessive 48 (MRT 48) (OMIM 616269) is a recessive syndromic disorder characterized by progressive tremors, speech impairment, and behavioral problems. In the present study, we highlight a family with a case of MRT 48. The index patient was second born to healthy consanguineous parents with a history of intellectual disability. Whole exome sequencing of the patient was performed, which revealed a homozygous c.1693T>C;p.(Tyr565His) variant in the SLC6A17 gene. The variant segregated in the extended family with the phenotype. This study broadens the genotypic spectrum of SLC6A17 variants.
AbstractIntellectual Disability Medicine, Department of General Practice, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands The manuscript submitted does not contain information about medical device(s)/drug(s). No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.
Journal of Basic Research in Medical Sciences · 2017 · 0 citations · open access
The prevalence of chromosomal translocation t (1; 4) (p21; p14) in Iranian patients with mental disability
AbstractIntroduction: Intellectual disability or intellectual retardation is a condition in which total mental functioning is distinctively below average and there are disabilities in adaptive behaviors during growth. According to the definition of American Mental Disability Community in 1992 a person is considered intellectually disabled if he or she has an IQ (intelligence quotient) of less than 70 and has a limitation in one or multiple adaptive skills. There are many different causes of intellectual disability that one of them is the genetically and chromosomal abnormalities. The aim of this paper was to study translocation breakout t (1; 4) (p21; p14) in a number of mental retardation patients in Iran. Materials and methods: This descriptive study was carried out on 100 persons with light mental disability by using cytogenetic methods. Lymphocytes were cultured in the dedicated environment by G-Banding karyotype of each person after obtaining patient's blood sample. The data were statistically analyzed by logistic regression. Results: The findings showed that none of the patients with a mental disability was afflicted to the chromosomal translocation, (1; 4) (p21; p14).
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.
