DeCure for Intellectual disability, autosomal dominant 11
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, autosomal dominant 11 — 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 11 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 11 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
Three unrelated consanguineous families were found with deleterious homozygous variants in the NSUN6 gene. Two of the variants are predicted to be loss-of-function; one leads to absence of NSUN6 via nonsense-mediated decay, the other encodes a protein that does not fold correctly. A missense variant in the third family lost enzymatic activity and cannot bind the methyl donor S-adenosyl-L-methionine. Affected individuals present with developmental delay, intellectual disability, motor delay, and behavioural anomalies. Homozygous ablation of the NSUN6 ortholog in Drosophila caused locomotion and learning impairment. The authors conclude that biallelic pathogenic variants in NSUN6 cause one form of autosomal recessive intellectual disability.
Intellectual disability has a global prevalence of about 6 to 8 percent. Most cohort genetic studies on intellectual disability have revealed the important contribution of de novo variants, but autosomal recessive forms account for most molecular bases in inbred populations. Fragile X syndrome, the most common inherited form, has been proposed as a benchmark for CNS drug discovery aimed at treating neurodevelopmental disorders rather than merely relieving symptoms.
One review proposes homoeopathic management for intellectual disability disorder, stating that homoeopathic medicine will remove the disease from the root cause. No trial data, response rates, or survival figures are provided in that review. No drug is tested in any of the abstracts for autosomal dominant intellectual disability 11 specifically.
What is still missing: any clinical trial testing a drug for autosomal dominant intellectual disability 11; any patient stratification by genetic subtype; any funding for a targeted therapy development programme. The NSUN6 finding is purely genetic and has not been translated into a treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMJ · 2014 · 26 citations
Drug treatments in people with intellectual disability and challenging behaviour
AbstractTime to rethink?
Do we still need to be reminded that the drug treatment of people with intellectual disability is often prolonged and not without dangers? We probably do. Drug treatment has been a mainstay for managing a common syndrome subsumed under the label “aggressive challenging behaviour” since chlorpromazine was first introduced for its treatment over 40 years ago.
We have no fundamental criticism of the transfer of a successful treatment for one disorder in general psychiatry to the same disorder in people who are intellectually disabled. However, challenging behaviour has no equivalent in general psychiatry, so there is no treatment to transfer. Challenging behaviour is the most common disturbance requiring intervention in intellectual disability services, but it does not have proper diagnostic status in standard psychiatric classifications.
Yet this does not inhibit the wholesale import of adult psychopharmacology into its management. Psychotropic medication in its many forms — mainly antipsychotics, sedatives and tranquillisers, antidepressants, and mood stabilisers—has seen extensive off-label prescribing for the past 50 years. Thus, a recent population based cohort study of 1023 adults with intellectual …
Genetics in Medicine · 2023 · 20 citations · open access
Biallelic variants in NSUN6 cause an autosomal recessive neurodevelopmental disorder
AbstractPURPOSE: 5-methylcytosine RNA modifications are driven by NSUN methyltransferases. Although variants in NSUN2 and NSUN3 were associated with neurodevelopmental diseases, the physiological role of NSUN6 modifications on transfer RNAs and messenger RNAs remained elusive. METHODS: We combined exome sequencing of consanguineous families with functional characterization to identify a new neurodevelopmental disorder gene. RESULTS: We identified 3 unrelated consanguineous families with deleterious homozygous variants in NSUN6. Two of these variants are predicted to be loss-of-function. One maps to the first exon and is predicted to lead to the absence of NSUN6 via nonsense-mediated decay, whereas we showed that the other maps to the last exon and encodes a protein that does not fold correctly. Likewise, we demonstrated that the missense variant identified in the third family has lost its enzymatic activity and is unable to bind the methyl donor S-adenosyl-L-methionine. The affected individuals present with developmental delay, intellectual disability, motor delay, and behavioral anomalies. Homozygous ablation of the NSUN6 ortholog in Drosophila led to locomotion and learning impairment. CONCLUSION: Our data provide evidence that biallelic pathogenic variants in NSUN6 cause one form of autosomal recessive intellectual disability, establishing another link between RNA modification and cognition.
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.
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.
Majmaah Journal of Health Sciences · 2021 · 0 citations · open access
Review On Clinical And Molecular Genetics Of Autosomal Recessive Intellectual Disability
AbstractIntellectual disability (ID) is a relatively common phenotype with multiple etiologies. Recent progress in the genetics of ID greatly expanded our understanding of the biological defects underlying this clinical entity. While most published cohort genetic studies on ID revealed the important contribution of de novo (germline or postzygotic) variants, we focused in this study of autosomal recessive ID (ARID), that account for most of the molecular bases in ID cases in inbred populations. We discussed the current state of ARID from a clinical, molecular and genetics standpoints.
Dusunen Adam The Journal of Psychiatry and Neurological Sciences · 2020 · 0 citations · open access
10q distal trisomy and 15q monosomy as a rare genetic cause for intellectual disability
AbstractIntellectual disability (ID) is defined as a neurodevelopmental disorder. The prevalence is 1% to 3%. Genetic factors strongly contribute to the etiology of ID; however, the origin remains unknown in up to 60% of the cases. De novo mutations are a common genetic cause in sporadic cases of ID. This report describes the cases of 2 siblings with distinctive phenotypical features and neurodevelopmental disorders with an unbalanced translocation, (46,XX,der[15]t[10;15][q24.3;26.1]mat), resulting in trisomy of the long arm of chromosome 10 and monosomy of the long arm of chromosome 15. The cases are thought to be associated with distal trisomy 10q syndrome and monosomy 15q syndrome. Both trisomy 10q and monosomy 15q syndromes are rare diseases with distinctive clinical profiles.
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.
