DeCure for Intellectual developmental disorder, autosomal dominant 64
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for intellectual developmental disorder, autosomal dominant 64 — 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 developmental disorder, autosomal dominant 64 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 developmental disorder, autosomal dominant 64 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 abstracts describe several genetic causes of intellectual disability but report no drug that alters the underlying cognitive deficit. A 2011 review states that intellectual disability was considered immutable and that current medical practice only relieves symptoms, though it raises the possibility that future treatments might target the core deficit, using Fragile X syndrome as a benchmark. No clinical trial data for any disease-modifying drug in autosomal dominant intellectual disability are provided in these abstracts.
One 2022 case report describes a child with a ZBTB18 gene variant (autosomal dominant mental disorder type 22) whose epileptic seizures were controlled for nearly half a year with levetiracetam and rehabilitation, and whose psychomotor and language development improved. A 2023 case series of eight children with SYNGAP1 gene mutations (autosomal dominant mental retardation type 5) reports that among 33 children with a history of epileptic medication, 28 (85%) showed response to valproic acid and 16 (48%) achieved complete seizure control with valproic acid monotherapy or combined therapy. These are anticonvulsant effects, not treatments for the intellectual disability itself.
Other abstracts report single cases of pathogenic variants in TRIP12 and SLC6A17 genes, and a 2022 review notes that there are limited pharmacological interventions for intellectual disability and limited mouse models. No abstract describes a drug that improves cognitive function in any form of autosomal dominant intellectual disability.
What is still missing: any clinical trial that tests a drug specifically for the cognitive or adaptive deficits of autosomal dominant intellectual disability, funding for such trials, and patient stratification by the specific gene mutation. The existing reports only address seizure control in a subset of patients.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
[Analysis of clinical features and ZBTB18 gene variant in a child with autosomal dominant mental disorder type 22].
AbstractOBJECTIVE: To analyze the clinical characteristics and ZBTB18 gene variant in a child with epilepsy and global developmental delay. METHODS: Clinical data and laboratory examination of the patient were reviewed. Whole exome sequencing (WES) was also carried out for the family trio. RESULTS: The main manifestations of the child included global developmental delay, short stature, epileptic seizures. EEG revealed frequent occurrence of sharp (slow) waves in the right central region during sleeping, with sharp waves occasionally seen in the frontal and right posterior temporal regions. Cranial MRI has shown no obvious abnormality. WES has identified a de novo pathogenic variant in the ZBTB18 gene [NM_205768.3: exon 2: c.1282_1283del (p.Phe428Leufs*72)]. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PVS1_Moderate+PM2_Supporting). Following treatment with levetiracetam and rehabilitation, the seizures have been controlled for nearly half a year, with improvement of the psychomotor and language development. So far 28 children have been discovered with ZBTB18 gene mutations, and there was a significant difference in the clinical phenotypes of motor retardation, language retardation and epilepsy between those harboring frameshift/nonsense mutations and missense mutations. CONCLUSION: The c.1282_1283del (p.Phe428leufs *72) variant of the ZBTB18 probably underlay the autosomal dominant mental disorder type 22 in this child. Compared with missense mutations, frameshift/nonsense mutations may predispose more to motor retardation, delayed language development and epilepsy.
[Autosomal dominant mental retardation type 5 caused by <i>SYNGAP1</i> gene mutations: a report of 8 cases and literature review].
AbstractOBJECTIVES: gene mutations. METHODS: gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University. RESULTS: gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy. CONCLUSIONS: gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.
[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.
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.
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.
American Journal of Psychiatry and Neuroscience · 2025 · 0 citations · open access
From Genetics to Psychiatry: Long-Term Psychiatric Management of Williams Syndrome with a Rare Variant of Congenital Adrenal Hyperplasia
AbstractThis case report presents a 19-year-old male with an exceptionally rare co-occurrence of Williams-Beuren Syndrome (WBS) and 17α-hydroxylase deficiency, a form of congenital adrenal hyperplasia (CAH). Diagnosed with CAH in infancy due to hypertension, hypokalaemia, and ambiguous genitalia, and later confirmed to have WBS via fluorescence in situ hybridization (FISH), the patient exhibited global developmental delays, intellectual disability, recurrent seizures, and poor medication adherence. Psychiatric referral at age 18 was prompted by escalating aggression, self-injurious behaviour, and functional decline. A multidisciplinary intervention was initiated, combining behavioural therapy based on the Antecedent-Behaviour-Consequence (ABC) framework, low-dose risperidone, psychoeducation for caregivers, and vocational rehabilitation. Over six months, the patient demonstrated marked improvement in aggression, seizure control, and compliance with daily routines. He remained seizure-free on sodium valproate and began contributing to household income through structured vocational engagement. This case underscores the importance of integrated psychiatric care in managing syndromic intellectual disability, particularly when compounded by rare endocrine disorders. The estimated statistical frequency of this genetic overlap is approximately 1 in 500 million, posing unique diagnostic and therapeutic challenges. The report highlights the need for early genetic evaluation, coordinated interdepartmental care, and family-centered interventions to optimize outcomes. It also emphasizes the utility of structured behavioural frameworks and low-dose antipsychotics in managing irritability and aggression in syndromic populations. In resource-limited settings, sustained caregiver involvement and interdisciplinary collaboration are critical to improving quality of life and long-term prognosis. This case advocates for enhanced training in syndromic psychiatry and integrated care models to address the complex needs of individuals with overlapping genetic and endocrine conditions.
Sage Journals Data · 2024 · 0 citations · open access
Navigating the outcome maze: a scoping review of outcomes and instruments in clinical trials in genetic neurodevelopmental disorders and intellectual disability
AbstractBackground:Individuals with genetic neurodevelopmental disorders (GNDs) or intellectual disability (ID) are often affected by complex neuropsychiatric comorbidities. Targeted treatments are increasingly available, but due to the heterogeneity of these patient populations, choosing a key outcome and corresponding outcome measurement instrument remains challenging.Objectives:The aim of this scoping review was to describe the research on outcomes and instruments used in clinical trials in GNDs and ID.Eligibility criteria:Clinical trials in individuals with GNDs and ID for any intervention over the past 10 years were included in the review.Sources of evidence:MEDLINE, PsycINFO, and Cochrane CENTRAL were searched. Titles and abstracts were independently screened for eligibility with a subsample of 10% double-screening for interrater reliability. Data from full texts were independently reviewed. Discrepancies were discussed until consensus was reached.Charting methods:Information was recorded on patient populations, interventions, designs, outcomes, measurement instruments, and type of reporter when applicable. Qualitative and descriptive analyses were performed.Results:We included 312 studies reporting 91 different outcomes, with cognitive function most frequently measured (28%). Various outcome measurement instruments (<i>n</i> = 457) were used, with 288 in only a single clinical trial. There were 18 genetic condition-specific instruments and 16 measures were designed ad-hoc for one particular trial. Types of report included proxy-report (39%), self-report (22%), clinician-report (16%), observer-report (6%), self-assisted report (1%), or unknown (16%).Conclusion:This scoping review of current practice reveals a myriad of outcomes and outcome measurement instruments for clinical trials in GNDs and ID. This complicates generalization, evidence synthesis, and evaluation. It underlines the need for consensus on suitability, validity, and relevancy of instruments, ultimately resulting in a core outcome set. A series of steps is proposed to move from the myriad of measures to a more unified approach.
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.
