DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder maps to a 4-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 adnp-related multiple congenital anomalies - intellectual disability - autism spectrum disorder 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
CD38 molecule (CD38) — CD38 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 cxrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2O3S · 1.5 Å · ligand CYCLIC ADENOSINE DIPHOSPHATE-RIBOSE (CXR). Experimental structure, not a prediction.
What the evidence adds up to
ADNP mutations cause Helsmoortel-Van der Aa syndrome, a syndromic form of autism. A 2020 scoping review of ten neurodevelopmental genes, including ADNP, found that reports of cognitive and developmental outcomes in affected individuals have been variable. The review identified significant gaps in understanding the natural history of these conditions and noted a lack of longitudinal data. A 2023 review confirmed that heterozygous, predicted loss-of-function ADNP mutations inevitably result in the clinical presentation of this syndrome. ADNP is a zinc finger DNA-binding protein involved in chromatin remodelling, associated with the SWI/SNF complex and the ChAHP complex, and has recently been shown to possess R-loop processing activity. The review concluded that it remains unclear how abnormalities in chromatin remodelling relate to the pleiotropic clinical features seen in affected individuals.
A 2025 review on precision diagnostics and therapeutics for rare genetic neurodevelopmental disorders noted that current therapeutic modalities including small molecule drugs, gene therapies, and antisense oligonucleotide therapies have emerged and shown promise in preclinical trials, with some drugs gaining FDA approval. However, translational challenges are extensive, especially for identifying biomarkers of drug effects in the central nervous system. The review also stated that limited access to genetic testing remains a barrier towards precision therapeutics for rare neurodevelopmental disorders, and that pre-clinical investigations face obstacles when translating to human subjects.
No clinical trial data for any drug in ADNP syndrome were presented in these abstracts. No concrete survival or response rates were reported for any intervention. The 2020 review explicitly stated that future research focusing on barriers to assessment, development of modified assessment tools, and collection of longitudinal data is needed to inform evaluations of treatment. What is still missing for ADNP syndrome specifically are longitudinal natural history studies, validated outcome measures, identified biomarkers for drug effects, and any completed or ongoing clinical trials testing a therapeutic agent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 2020 · 61 citations
Description of neurodevelopmental phenotypes associated with 10 genetic neurodevelopmental disorders: A scoping review
AbstractNeurodevelopmental disorders (NDDs) are a heterogeneous group of conditions including intellectual disability, global developmental delay, autism spectrum disorder, and attention deficit hyperactivity disorder. Advances in genetic diagnostic technology have led to the identification of a number of NDD-associated genes, but reports of cognitive and developmental outcomes in affected individuals have been variable. The objective of this scoping review is to synthesize available information pertaining to the developmental outcomes of individuals with pathogenic variants in ten emerging recurrent NDD-associated genes identified from large scale sequencing studies; ADNP, ANKRD11, ARID1B, CHD2, CHD8, CTNNB1, DDX3X, DYRK1A, SCN2A, and SYNGAP1. After a comprehensive search, 260 articles were selected that reported on neurodevelopmental measures or diagnoses. We identify the spectrum of developmental outcomes for each genetic NDD, including prevalence of intellectual disability, frequency of co-morbid NDDs such as ADHD and autism, and commonly reported medical issues that can help inform diagnosis and treatment. There are significant gaps in our understanding of the natural history of these conditions. Future research focusing on barriers to assessment, the development of modified assessment tools appropriate for long-term outcomes in genetic NDD, and collection of longitudinal data will increase understanding of prognosis in these conditions and inform evaluations of treatment.
Clinical Epigenetics · 2023 · 59 citations · open access
Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism
AbstractBACKGROUND: Individuals affected with autism often suffer additional co-morbidities such as intellectual disability. The genes contributing to autism cluster on a relatively limited number of cellular pathways, including chromatin remodeling. However, limited information is available on how mutations in single genes can result in such pleiotropic clinical features in affected individuals. In this review, we summarize available information on one of the most frequently mutated genes in syndromic autism the Activity-Dependent Neuroprotective Protein (ADNP). RESULTS: Heterozygous and predicted loss-of-function ADNP mutations in individuals inevitably result in the clinical presentation with the Helsmoortel-Van der Aa syndrome, a frequent form of syndromic autism. ADNP, a zinc finger DNA-binding protein has a role in chromatin remodeling: The protein is associated with the pericentromeric protein HP1, the SWI/SNF core complex protein BRG1, and other members of this chromatin remodeling complex and, in murine stem cells, with the chromodomain helicase CHD4 in a ChAHP complex. ADNP has recently been shown to possess R-loop processing activity. In addition, many additional functions, for instance, in association with cytoskeletal proteins have been linked to ADNP. CONCLUSIONS: We here present an integrated evaluation of all current aspects of gene function and evaluate how abnormalities in chromatin remodeling might relate to the pleiotropic clinical presentation in individual"s" with Helsmoortel-Van der Aa syndrome.
Pediatric Research · 2025 · 6 citations · open access
Precision diagnostic and therapeutic interventions in rare genetic neurodevelopmental disorders
AbstractNeurodevelopmental disorders (NDDs) include a broad spectrum of phenotypes spanning from intellectual disability (ID) to developmental delay (DD) and autism spectrum disorder (ASD). As neurodevelopmental phenotypes are a common presenting feature of an underlying genetic condition, professional medical organizations recommend genetic testing for all individuals with a NDD. When testing is pursued, identified genetic differences can lead to personalized clinical management with early diagnosis supporting the development of surveillance and intervention for co-occurring adverse health outcomes. Despite this, barriers to testing have prevented individuals from receiving a genetics referral and testing. Current therapeutic modalities including small molecule drugs, gene therapies, and antisense oligonucleotide therapies have emerged and shown promise in preclinical trials with therapeutic drugs gaining FDA approval. However, translational challenges are extensive, especially for identifying biomarkers of drug effects in the CNS. In this review, we discuss diagnostic approaches and clinical utility of genetic testing for rare genetic neurodevelopmental disorders, emerging development of individualized therapies, and progress for current therapeutics in addition to challenges with clinical translation and delivery. We will highlight opportunities for early diagnosis and treatment that are steadily gaining ground in favor of optimizing long-term health outcomes and improving quality of life for neurodiverse individuals. IMPACT: The path from genomics to therapeutics for neurodevelopmental disorders continues to present multiple opportunities and challenges. While emerging genome-wide sequencing and gene editing technologies deliver increased diagnostic yields and alternatives to life-long small molecule therapies, clinical translation has been challenging due to inherent cost and genetic heterogeneity. Limited access to genetic testing despite practice guidelines remains a barrier towards precision therapeutics for rare neurodevelopmental disorders, while pre-clinical investigations face obstacles when translating to human subjects. This review will summarize the impact of existing successes in diagnosis and therapeutics for neurodevelopmental disorders while highlighting ongoing challenges and areas of future opportunities.
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.
