DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability, X-linked 81 — 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, X-linked 81 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, x-linked 81 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
In 2016 a single missense mutation, A789V in IQSEC2, was identified as the cause of X-linked intellectual disability in the MRX78 family, which included six affected males and seven affected females. The mutation disrupts the catalytic Sec7 domain of the encoded protein, and functional assays showed that the recombinant mutant protein could not catalyse GDP-GTP exchange on Arf6 as efficiently as the wild-type protein. No other families or individuals with this specific mutation have been reported in the abstracts provided, and no treatment or intervention is mentioned.
A 2021 systematic review of physical activity correlates in people with intellectual disability found only three consistent correlates, all in adults. Older age was associated with decreased physical activity in 7 of 11 studies (64%), more severe intellectual disability in 9 of 9 studies (100%), and the presence of physical mobility problems in 3 of 4 studies (75%). No consistent correlates were identified for children, adolescents, or older adults. The review covered 26,456 participants but found the evidence base insufficient to guide intervention design for younger or older age groups.
A 2020 study evaluated expressive language sampling as a potential outcome measure for treatment trials in fragile X syndrome, enrolling 106 individuals aged 6 to 23 years with IQs in the intellectual disability range. The abstract does not report any drug or treatment being tested, only the feasibility and psychometric properties of the language sampling procedure. No results on practice effects, test-retest reliability, or construct validity are given in the abstract provided.
What is still missing is any clinical trial testing a drug for IQSEC2-related intellectual disability, any validated outcome measure specific to this mutation, and any understanding of whether physical activity interventions or language sampling procedures would be useful endpoints in such a trial. Patient stratification by mutation type, age, and severity of intellectual disability would be needed, and funding for natural history studies and preclinical work remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Molecular Neuroscience · 2016 · 27 citations · open access
Novel Missense Mutation A789V in IQSEC2 Underlies X-Linked Intellectual Disability in the MRX78 Family
AbstractDisease gene discovery in neurodevelopmental disorders, including X-linked intellectual disability (XLID) has recently been accelerated by next-generation DNA sequencing approaches. To date, more than 100 human X chromosome genes involved in neuronal signaling pathways and networks implicated in cognitive function have been identified. Despite these advances, the mutations underlying disease in a large number of XLID families remained unresolved. We report the resolution of MRX78, a large family with six affected males and seven affected females, showing X-linked inheritance. Although a previous linkage study had mapped the locus to the short arm of chromosome X (Xp11.4-p11.23), this region contained too many candidate genes to be analyzed using conventional approaches. However, our X-chromosome exome resequencing, bioinformatics analysis and inheritance testing revealed a missense mutation (c.C2366T, p.A789V) in IQSEC2, encoding a neuronal GDP-GTP exchange factor for Arf family GTPases (ArfGEF) previously implicated in XLID. Molecular modeling of IQSEC2 revealed that the A789V substitution results in the insertion of a larger side-chain into a hydrophobic pocket in the catalytic Sec7 domain of IQSEC2. The A789V change is predicted to result in numerous clashes with adjacent amino acids and disruption of local folding of the Sec7 domain. Consistent with this finding, functional assays revealed that recombinant IQSEC2(A789V) was not able to catalyze GDP-GTP exchange on Arf6 as efficiently as wild-type IQSEC2. Taken together, these results strongly suggest that the A789V mutation in IQSEC2 is the underlying cause of XLID in the MRX78 family.
Disability and Rehabilitation · 2021 · 26 citations
Physical activity correlates in children and adolescents, adults, and older adults with an intellectual disability: a systematic review
AbstractPURPOSE: Understanding enablers of and barriers for physical activity (PA) participation in people with intellectual disability (ID) is an essential first step to develop effective interventions. This systematic review examined correlates of PA across the socio-ecological model (i.e., intra-personal, inter-personal, environmental and policy level) in people with ID across the lifespan. MATERIAL AND METHODS: Major electronic databases were searched from inception until 15 February 2021. Keywords included "physical activity" or "exercise" and "intellectual disability" or "mental retardation." A summary coding was used to analyze the data for adolescents (<18 years), adults (18 < 50 years), and older adults (50≤ years). RESULTS: = 26,456), only three consistent (i.e., reported in four or more studies) correlates were identified. In adults, older age (7/11, 64%), more severe ID (9/9, 100%) and the presence of physical mobility problems (3/4, 75%) were associated with decreased PA. From 38 correlates identified, no consistent correlates were identified for children and adolescents and older people. CONCLUSIONS: Despite the abundance of evidence of the PA benefits for people with ID, we only found consistent evidence for three correlates reliably being related to PA in adults with ID. More research, particularly among young and older people is urgently needed.IMPLICATIONS FOR REHABILITATIONMore severe intellectual disability is an important barrier for being active in adults with intellectual disability.Presence of physical health problems is an important barrier for being active in adults with intellectual disability.
Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity
AbstractAbstract Background The evaluation of treatment efficacy for individuals with fragile X syndrome (FXS) or intellectual disability (ID) more generally has been hampered by the lack of adequate outcome measures. We evaluated expressive language sampling (ELS) as a procedure for generating outcome measures for treatment research in FXS. We addressed: (a) feasibility, (b) practice effects over two administrations, (c) test-retest reliability over the repeated administrations, and (d) construct validity. We addressed these issues for the full sample as well as for subgroups defined by age, IQ, and ASD status. Methods Participants were 106 individuals with FXS between ages 6 and 23 years who had IQs within the range of intellectual disability (IQ
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.
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.
