DeCure for Intellectual disability, autosomal dominant 58
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, autosomal dominant 58 — 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 58 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 58 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
SET nuclear proto-oncogene (SET) — SET 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2E50 · 2.3 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Three unrelated consanguineous families with deleterious homozygous variants in NSUN6 were identified in a 2023 study. Two variants are predicted loss-of-function; one maps to the first exon and is predicted to lead to absence of NSUN6 via nonsense-mediated decay, the other maps to the last exon and 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 led to locomotion and learning impairment. The authors conclude that biallelic pathogenic variants in NSUN6 cause one form of autosomal recessive intellectual disability.
A 2021 case report describes a patient with intellectual disability carrying a heterozygous nonsense c.40C>T (p.Arg14X) variant of the TRIP12 gene, de novo in origin. The variant was unrecorded in the Human Gene Mutation Database and was predicted pathogenic (PVS1+PS2+PP3). The patient was diagnosed with autosomal dominant intellectual disability due to this TRIP12 variant.
A 2011 review on Fragile X syndrome states that intellectual disability is considered an immutable condition and that current medical practices aim at relieving symptoms, not altering underlying cognitive deficits. The review notes that pharmaceutical therapies targeting Fragile X syndrome may become a benchmark for CNS drug discovery seeking cures for neurodevelopmental disorders. A 2008 textbook describes adaptations of DSM-IV-TR diagnostic criteria for psychiatric conditions in people with intellectual disability, providing a review of scientific literature and evidence strength ratings.
No drug treatment is tested or recommended in any of these abstracts. What is missing for autosomal dominant intellectual disability type 58 specifically is any clinical trial, any drug-repurposing study, any patient stratification strategy, and any funding directed at this particular genetic subtype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Mental Illness and Intellectual DisabilityMental Illness and Intellectual Disability
AbstractThe Diagnostic Manual—Intellectual Disability: A Textbook of Diagnosis of Mental Disorders in Persons with Intellectual Disability (DM–ID) provides adaptations of the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM–IV–TR; American Psychiatric Association, 2000) that will facilitate more accurate diagnosis of psychiatric conditions in people with intellectual disability (ID). The text also provides a review of the relevant scientific literature for each condition and a rating of the strength of the evidence supporting assertions in the literature. The volume is the product of considerable effort; the four editors were assisted in their task by a 10member advisory board, seven external peer reviewers, dozens of Diagnostic Manual—Intellectual Disability: A
[Intellectual disability due to heterozygous c.40C>T variant of TRIP12 gene in a patient].
AbstractOBJECTIVE: To explore the genetic basis for a patient with intellectual disability. METHODS: Whole exome sequencing and Sanger sequencing were carried out for the patient. The result was verified in her family. RESULTS: DNA sequencing revealed that the patient has carried a heterozygous nonsense c.40C>T (p.Arg14X) variant of the TRIP12 gene, which was de novo in origin. The variant was unrecorded in the Human Gene Mutation Database. Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+ PS2+ PP3). CONCLUSION: The patient was diagnosed with autosomal dominant intellectual disability due to heterozygous c.40C>T variant of the TRIP12 gene.
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.
