DeCure for Microcephaly, seizures, and developmental delay
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for microcephaly, seizures, and developmental delay — 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 moduleMicrocephaly, seizures, and developmental delay 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 microcephaly, seizures, and developmental delay 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
polynucleotide kinase 3'-phosphatase (PNKP) — PNKP 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2BRF · 1.4 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2007 study in rats bred to be seizure-prone (FAST) compared to seizure-resistant (SLOW) found that two genes were significantly underexpressed in the brains of seizure-prone embryos at embryonic day 21: Apolipoprotein E (APOE) and the beta2 subunit of the voltage-gated sodium channel (SCN2beta). Most of the 112 neurodevelopmental genes examined showed near equivalent expression between the strains. The authors note that these two transcripts have no known interactions during embryogenesis but have been independently linked to seizure disposition and neurodevelopmental aberrations leading to epilepsy. This work is preclinical and does not test any drug.
A 2024 retrospective study of 21 paediatric patients with epileptic encephalopathies who received pulse intravenous methylprednisolone (IVMP) therapy reported a responder rate (seizure reduction greater than 50%) of 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. The best outcomes were seen in patients with genetic epilepsy and those with encephalopathy related to electrical status epilepticus during slow-wave sleep (ESES). All patients showed improved quality of life at last follow-up, and no relevant adverse events were observed. The sample is small and the study is retrospective, with no control group.
A 2025 study of 247 children with global developmental delay and microcephaly (median age 3.3 years) found that seizures were the most common co-morbidity, affecting 154 children (62.3%). Perinatal asphyxia was noted in 83 children (33.6%). Abnormal MRI was found in 187 children (75.7%), with white matter lesions the most common finding (155 children, 62.7%). Children with birth asphyxia had significantly more MRI abnormalities in the ventricles, corpus callosum, and gray and white matter. This study describes the clinical and radiological profile but does not test any treatment.
What is still missing are prospective, controlled trials of any drug for this combination of microcephaly, seizures, and developmental delay. The IVMP data is limited to a single small retrospective series in epileptic encephalopathies, not specifically in children with microcephaly and global developmental delay. No trial has stratified patients by the genetic or imaging findings that these studies identify as relevant. Funding for such trials, and for the development of animal models that combine these features, 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.
Epilepsia · 2007 · 14 citations
Neurodevelopment in Seizure‐prone and Seizure‐resistant Rat Strains: Recognizing Conflicts in Management
AbstractCytoarchitectural alterations during central nervous system (CNS) development are believed to underlie aberrations in brain morphology that lead to epilepsy. We have recently reported marked reductions in hippocampal and white matter volumes along with relative ventriculomegaly in a rat strain bred to be seizure-prone (FAST) compared to a strain bred to be seizure-resistant (SLOW) (Gilby et al., 2002, American Epilepsy Society 56th Annual Meeting). This study was designed to investigate deviations in gene expression during late-phase embryogenesis within the brains of FAST and SLOW rats. In this way, we hoped to identify molecular mechanisms operating differentially during neurodevelopment that might ultimately create the observed differences in brain morphology and/or seizure susceptibility. Using Superarray technology, we compared the expression level of 112 genes, known to play a role in neurodevelopment, within whole brains of embryonic day 21 (E21) FAST and SLOW rats. Results revealed that while most genes investigated showed near equivalent expression levels, both Apolipoprotein E (APOE) and the beta2 subunit of the voltage-gated sodium channel (SCN2beta) were significantly underexpressed in brains of the seizure-prone embryos. Currently, these transcripts have no known interactions during embryogenesis; however, they have both been independently linked to seizure disposition and/or neurodevelopmental aberrations leading to epilepsy. Thus, alterations in the timing and/or degree of expression for APOE and SCN2beta may be important to developmental cascades that ultimately give rise to the differing brain morphologies, behaviors, and/or seizure vulnerabilities that characterize these strains.
Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration
AbstractBackground: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Variables significantly predicting favorable outcome were etiology (p =0,0475) and epilepsy type (p =0,0475), with the best outcome achieved in patients with genetic epilepsy and those with encephalopathy related to electrical status epilepticus during slow-wave sleep (ESES). All patients evidenced improved QoL at the last follow-up. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and high tolerability of IVMP pulse therapy in patients with EE. Genetic epilepsy and ESES were positive predictor of favorable clinical outcome. QOL, EEG features and posture-motor development showed an improving trend as well. IVMP pulse therapy should be considered earlier in patients with EE.
Clinical Epidemiology and Global Health · 2025 · 0 citations · open access
Clinicoradiological profile of children presenting with global developmental delay and microcephaly
AbstractObjective To study the clinical and radiological profile of children with Global developmental delay and microcephaly and correlate the clinical findings with structural brain lesions identified through neuroimaging. Methods This single-centre study, conducted from 1 st April 2017 to 31 st March 2022, included 247 children with global developmental delay and microcephaly. Data was collected using a pre-designed proforma, documenting presenting complaints, birth and developmental history, growth patterns, physical and neurological examination results, associated co-morbidities with neuroimaging findings. Results Among the 247 children, 197 (79.8%) were under 5 years, and 50 (20.2%) were over 5 years, with a male-to-female ratio of 1.5:1 and a median age of 3.3 years(1.1, 5). Perinatal asphyxia was noted in 83 children (33.6%). A total of 145 children under 5 years (58.7%) were malnourished, and 14 children over 5 years (28%) were underweight. Seizures were the most common co-morbidity, affecting 154 children (62.3%), visual abnormalities were detected in 118 children, (47.8%) and hearing abnormalities in approximately one-sixth (15%). Abnormal MRI was noted in 187 (75.7%), with white matter lesions being the most common, observed in 155 children (62.7%). Children born with birth asphyxia displayed significant MRI abnormalities in the ventricles, corpus callosum, and gray and white matter (p<0.05). Conclusion This study outlines the complex clinicoradiological profile of children with GDD and microcephaly, highlighting common MRI abnormalities such as white matter and corpus callosum lesions. Seizures and perinatal factors significantly affect MRI findings, underscoring the need for comprehensive evaluation and management strategies.
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.
