DeCure for Intellectual disability, autosomal recessive 27
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, autosomal recessive 27 — 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 recessive 27 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 recessive 27 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 with biallelic homozygous variants in NSUN6 were identified by exome sequencing. Two variants were predicted loss-of-function: one in the first exon expected to trigger nonsense-mediated decay, the other in the last exon producing a protein that does not fold correctly. The third family carried a missense variant that lost enzymatic activity and could not bind the methyl donor S-adenosyl-L-methionine. Affected individuals presented with developmental delay, intellectual disability, motor delay, and behavioural anomalies. Homozygous knockout of the NSUN6 ortholog in Drosophila caused locomotion and learning impairment. No drug intervention was tested in this study.
A 2011 review stated that intellectual disability was then considered an immutable condition, with medical practices aimed at symptom relief rather than altering underlying cognitive deficits. The same review noted that pharmaceutical therapies targeting Fragile X syndrome might become a benchmark for CNS drug discovery, but no specific drug or trial data were provided.
A 2021 case report described a single patient with a heterozygous de novo nonsense c.40C>T variant in TRIP12, classified as pathogenic by ACMG criteria. The patient was diagnosed with autosomal dominant intellectual disability. No treatment or drug was mentioned.
No drug has been tested in any of these studies for intellectual disability autosomal recessive 27 or for the TRIP12-related form. The NSUN6 finding is purely genetic and functional, with no therapeutic experiment. What is missing is any clinical trial, any drug candidate, any funding for translational work, and any patient stratification strategy that would allow a repurposing study to begin.
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.
[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.
