DeCure for Intellectual disability, autosomal dominant 39
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, autosomal dominant 39 — 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 moduleIntellectual disability, autosomal dominant 39 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 intellectual disability, autosomal dominant 39 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
The 2011 study identified a missense mutation (p.R617Q) in MED23 that cosegregated with nonsyndromic autosomal recessive intellectual disability in one family. 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 treatment was tested.
A 2025 study reported a homozygous c.1693T>C;p.(Tyr565His) variant in SLC6A17 in a Pakistani family with autosomal recessive intellectual disability (MRT48), identified by whole exome sequencing. The variant segregated with the phenotype in the extended family. No treatment was tested.
A 2014 study performed homozygosity mapping in 11 consanguineous Pakistani families multiplex for autosomal recessive intellectual disability. It identified 39 potential homozygosity-by-descent regions across families, with two families sharing an overlapping region on 7q11.21. No copy-number variations segregating with the phenotype were found. The study did not test any treatment.
Two 2022 reviews note that intellectual disability affects 1% to 8% of the global population and that pharmacological interventions remain limited. One review discusses homeopathic management but provides no trial data or evidence of efficacy. A 2011 review on Fragile X syndrome mentions the possibility that intellectual disability may become treatable but reports no tested intervention for MED23-related or SLC6A17-related intellectual disability.
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.
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.
Homozygosity mapping of autosomal recessive intellectual disability loci in 11 consanguineous Pakistani families
AbstractBACKGROUND: Autosomal recessive intellectual disability (ID) is genetically heterogeneous and most of the genes causing it remain undiscovered. OBJECTIVE: We have ascertained 11 consanguineous families multiplex for IDs in order to identify new loci for autosomal recessive genes for non-syndromic ID, or to aid pinpointing mutations in known causative gene/loci. Methodology Microarray genotyping (Affymatrix 250K) was performed to identify homozygosity-by-descent (HBD) in all affected families. RESULTS: Analysis of genotypes revealed 45 potential HBD regions across the families, although these may be rationalised down to 39. Two families share an overlapping HBD region on 7q11.21. In one family, X-linkage also looks plausible, and a new ID gene near the centromere may be a likely cause. In one family, no HBD region was found, and thus we exclude autosomal recessive mutation as the likely cause in this family. Copy-number variation (CNV) was also performed and revealed no CNVs, homozygous or heterozygous, segregating with the phenotype. CONCLUSION: The homozygous loci identified in this study might harbour candidate genes for ID in these studied families. Therefore, we are proceeding with next-generation sequencing analysis of the families, using whole-exome approaches, and anticipate that this will identify the causative gene/mutation within the identified HBD regions for many of the families studied here.
Borjeson-Forssman-Lehmann Syndrome: Clinical Features and Diagnostic Challenges
Abstractgene. The syndrome is characterized by short stature, obesity, hypogonadism, hypotonia, intellectual disability, distinctive facial features, fleshy ears, and finger and toe abnormalities. However, the diagnostic challenge in identifying BFLS remains a topic of interest. In this case report, we present the clinical characteristics of a proband with BFLS, highlighting the additional features of hypotonia, intellectual disability, and distinctive facial features. While no definitive treatment exists for BFLS, patients benefit from specialized education and ongoing supervision from early childhood through adulthood. Symptomatic treatment, including close follow-up, may be necessary for complications such as seizures and hearing problems. Mastectomy or testosterone replacement therapy may be considered on a case-by-case basis. Genetic counseling for X-linkage should be offered to affected families.
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.
International Journal of Homoeopathic Sciences · 2022 · 0 citations · open access
An overall review on intellectual disability disorder and its homoeopathic management
AbstractThe Intellectual Disability Disorder is found as a one of the clinical manifestations of the rare disorders which occupies a total prevalence of about 6 to 8% globally. The rare disorder is found to cause many of the chronic disabilities in which the intellectual disability disorder is one of them which has a drastic impact on the individual who is affected and their families and includes the health care system. The onset period of the rare disorder begins from the prenatal period into the late adulthood and it is being assessed that about the half of the individual affected are children [1]. The prime and the only purpose of this study undertaken is to find the effectiveness of the homoeopathic medicine in the treatment of the Intellectual Disability Disorder and also to alter their intellectual and the adaptive functions of the affected individual. The homoeopathic medicine will remove the disease from the root cause.
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.
Psychiatric And Psychological Treatment For A Woman Affected By Turner Syndrome, Obsessive Compulsive Disorder And Intellectual Disability : A Good Outcome
AbstractBackground:The intellectual development of patients affected by Turner Syndrome (TS) has a normal range. Some authors correlate mosaic karyotype TS to intellectual disability (ID). But small literature about correlations between TS and mental disorders can be found.Aims:To describe clinical and genetical features and treatment of a woman with TS associated with severe obsessive-compulsive disorder (OCD) and ID.Methods:A 22-year-old woman (S.) with mosaic karyotype TS 46,X,i(Xq)[40] \\ 45,X[10], ID and OCD was referred in 2014 for a severe and debilitating form of OCD.S. showed dwarfism, acoustic agnosia, amenorrhoea, pressured speech, borderline ID (WAIS-R = 73) with disability pension. OCD was shown since the age of 10. Compulsive cleaning (with a specific issue about leaves) was the most pervasive symptom (confirmed at SPAIDD-G) and compromised both her and her family quality of life. She was prescribed Fluvoxamine 300 mg and Olanzapine 10 mg then shifted to Aripiprazole 10 mg due to drowsiness and weight gain. Antipsychotic drug was due to the intensity of compulsions about leaves cleaning. Psychological support has been needed to manage symptoms particularly for her low intellectual resources. Results:Fluvoxamine + Aripiprazole treatment has been showing a good efficacy on OCD symptoms with no side effects. ID clearly influences her treatment management needing a psychotherapic approach. At Vineland Adaptive Behavior Scale (9/2018) she got good scores, over average for her ID level. Conclusions:A combination of psychiatric treatment and psychological support managed to reduce levels of symptoms and to find alternative behaviors to cope with the crisis.
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.
