DeCure for Intellectual developmental disorder, autosomal dominant 65
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for intellectual developmental disorder, autosomal dominant 65 — screening already-approved drugs against its 2-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 65 maps to a 2-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 65 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
OCRL inositol polyphosphate-5-phosphatase (OCRL) — OCRL 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3QBT · 2.0 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Intellectual developmental disorder, autosomal dominant 65 is not mentioned in any of the provided abstracts. The abstracts cover fragile X syndrome, general genetics of intellectual disability, SYNGAP1-related autosomal dominant mental retardation type 5, RHOBTB2-related epileptic encephalopathy, and SLC6A17-related autosomal recessive intellectual disability. No abstract discusses a drug or intervention for the specific condition named.
Among the conditions that are discussed, one abstract reports that in 48 children with SYNGAP1 mutations, 40 had seizures with a mean onset age of 31.4 months. Frameshift mutations accounted for 31% (15/48) and nonsense mutations for 40% (19/48). Of 33 children who received antiepileptic medication, 28 (85%) responded to valproic acid, and 16 (48%) achieved complete seizure control with valproic acid alone or in combination. The abstract does not report any effect on intellectual disability itself.
Another abstract describes a single family with a homozygous SLC6A17 variant causing autosomal recessive intellectual disability, but no treatment is tested. A 2024 abstract on RHOBTB2-related epileptic encephalopathy mentions development of an anti-sense oligonucleotide therapeutic but provides no human data, no response rates, and no survival figures. The 2011 abstract on fragile X syndrome states that intellectual disability was once considered immutable but that pharmaceutical therapies targeting fragile X syndrome might become a benchmark for CNS drug discovery; it reports no concrete results.
What is still missing for intellectual developmental disorder, autosomal dominant 65 specifically: no clinical trials, no identified drug, no patient cohort with that exact genetic diagnosis, and no funding directed at repurposing or developing a therapy for it. Even for the related SYNGAP1 condition, the only reported treatment effect is on seizures, not on cognition, and the sample is small (48 patients). No abstract provides evidence that any drug alters the course of intellectual disability in any of these disorders.
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.
Psychology and Personality · 2020 · 9 citations · open access
GENETICS OF INTELLECTUAL DISABILITY
AbstractIntellectual disability (ID) is a disorder with onset during the developmental period that includes both intellectual and adaptive functioning deficits in conceptual, social, and practical domains. The disorder has an overall general population prevalence of approximately 1%, and prevalence rates vary by age. Genetic factors play a major part in ID, especially in syndromic forms. The disorder is provoked by diverse variations of genome DNA – single nucleotide polymorphisms, single nucleotide variants, small insertions/deletions and copy number variations. The mutation can be transmitted from parents to children or happen de novo in a germline. Now there are found about 700 candidate ID genes: 100 X-linked, 200 autosomal-dominant and 400 autosomal-recessive. Non-syndromic forms of ID are associated with 92 candidate genes, of which 5 X-linked-dominant, 32 X-linked-recessive, 33 autosomal-dominant and 22 autosomal-recessive genes. Encoded proteins of most these genes take part in a formation and functioning of synapses. It should be noted that proposed ID candidate genes stand in need of a statistically significant under-statement on sufficiently large samples of patients and control individuals.
[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.
[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.
Genetics in Medicine Open · 2024 · 1 citations · open access
O42: Development of an anti-sense oligonucleotide therapeutic targeting RhoBTB2-related epileptic encephalopathy
AbstractRHOBTB2 encodes a member of the atypical Rho GTPase containing a GTPase domain and two tandem BTB domains. The BTB domains are involved in interacting with the Cullin3-dependent ubiquitin ligase complex, mediating ubiquitination, and recruiting substrates to the complex. Pathogenic de novo missense variants clustering in the BTB domains were reported to cause autosomal dominant developmental and epileptic encephalopathy 64 [DEE64; OMIM 618004]. DEE64 is a neurodevelopmental disorder characterized by onset of seizures within the first year of life, severe to profound intellectual disability, movement disorders, postnatal microcephaly, and nonspecific dysmorphic features.
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.
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.
