DeCure for Microcephaly, growth deficiency, seizures, and brain malformations
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for microcephaly, growth deficiency, seizures, and brain malformations — 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 moduleMicrocephaly, growth deficiency, seizures, and brain malformations 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 microcephaly, growth deficiency, seizures, and brain malformations 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
WDR4 tRNA N7-guanosine methyltransferase non-catalytic subunit (WDR4) — WDR4 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 sahdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8CTH · 3.3 Å · ligand S-ADENOSYL-L-HOMOCYSTEINE (SAH). Experimental structure, not a prediction.
What the evidence adds up to
A 2025 single-centre study of 247 children with global developmental delay and microcephaly found that 79.8% were under five years old, with a median age of 3.3 years. Seizures were the most common co-morbidity, affecting 62.3% of the children. Abnormal MRI findings were present in 75.7% of the cohort, with white matter lesions the most frequent abnormality, seen in 62.7%. Perinatal asphyxia was noted in 33.6% of children, and those with birth asphyxia had statistically significant MRI abnormalities in the ventricles, corpus callosum, and gray and white matter.
A 2008 screening study notes that pyridoxine dependent epilepsy is a rare autosomal-recessive metabolic disorder caused by a deficiency of 2-aminoadipic acid semialdehyde dehydrogenase activity, leading to secondary vitamin B6 deficiency. More than 120 cases had been reported at that time. The abstract states that besides seizures, mental retardation, and in some cases microcephaly and disturbed brain development, may occur.
A 2019 case report describes a nine-year-old girl with lissencephaly-pachygyria complex and hypoxic ischemic encephalopathy who presented with severe intellectual disability, seizures, autistic features, hyperactivity, and aggression. The report emphasises non-pharmacological interventions including family psycho-education, sensory and occupational therapy, and addressing caregiver burnout.
A 2018 review of the genetic determinants of brain size explains that microcephaly and megalencephaly are caused by mutations in a rapidly growing number of genes linked within critical cellular pathways impacting early brain development, with pathomechanistic links to cancer, body growth, and epilepsy. The review does not provide any treatment data. What remains missing across this literature is any controlled trial of a specific drug for microcephaly or its associated seizures and developmental delay, as well as systematic patient stratification by genetic aetiology or metabolic subtype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Dialogues in Clinical Neuroscience · 2018 · 104 citations · open access
From microcephaly to megalencephaly: determinants of brain size
AbstractExpansion of the human brain, and specifically the neocortex, is among the most remarkable evolutionary processes that correlates with cognitive, emotional, and social abilities. Cortical expansion is determined through a tightly orchestrated process of neural stem cell proliferation, migration, and ongoing organization, synaptogenesis, and apoptosis. Perturbations of each of these intricate steps can lead to abnormalities of brain size in humans, whether small (microcephaly) or large (megalencephaly). Abnormalities of brain growth can be clinically isolated or occur as part of complex syndromes associated with other neurodevelopmental problems (eg, epilepsy, autism, intellectual disability), brain malformations, and body growth abnormalities. Thorough review of the genetic literature reveals that human microcephaly and megalencephaly are caused by mutations of a rapidly growing number of genes linked within critical cellular pathways that impact early brain development, with important pathomechanistic links to cancer, body growth, and epilepsy. Given the rapid rate of causal gene identification for microcephaly and megalencephaly understanding the roles and interplay of these important signaling pathways is crucial to further unravel the mechanisms underlying brain growth disorders and, more fundamentally, normal brain growth and development in humans. In this review, we will (a) overview the definitions of microcephaly and megalencephaly, highlighting their classifications in clinical practice; (b) overview the most common genes and pathways underlying microcephaly and megalencephaly based on the fundamental cellular processes that are perturbed during cortical development; and (c) outline general clinical molecular diagnostic workflows for children and adults presenting with microcephaly and megalencephaly.
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.
Screening for pyridoxine dependent epilepsy (PDE) by Tandem Mass Spectrometry (HPLC-MS/MS)
AbstractIntroduction: Pyridoxine dependent epilepsy (PDE; MIM:266100) is a rare, auto-somal-recessive inborn error of metabolism. More than 120 cases have been reported up to now. Neonatal seizures are caused by a secondary vitamin B6 deficiency due to a lack of 2-aminoadipic acid semialdehyde dehydrogenase activity (2-AASA, allysine). Lysine degradation is disturbed. Besides seizures mental retardation, in some cases microcephaly and disturbed brain development may occur.
Journal of Indian Association for Child and Adolescent Mental Health · 2019 · 0 citations
Hyperactivity and autistic features in a child with lissencephaly-pachygyria complex with hypoxic ischemic encephalopathy
AbstractLissencephaly–pachygyria complex or spectrum is a rare malformation of cortical development characterised by neuronal migration defect and abnormal formation of cerebral gyri or convolutions. The main features of lissencephaly are abnormally thick cortex along with absent (agyria) or abnormally developed (pachygyria) cerebral convolutions making the brain appear smooth. We present a case of nine-year-old girl with lissencephaly-pachygyria complex with hypoxic ischemic encephalopathy. She presented with severe intellectual disability, seizures, autistic features with marked sensory issues, self-stimulating behaviors, hyperactivity and aggression. We describe the clinical manifestations and highlight the role of non-pharmacological interventions that include family psycho-education, sensory and occupational therapy, functional behavior analysis and therapy, and addressing caregiver burn-out.
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.
