DeCure for Severe neonatal-onset encephalopathy with microcephaly
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for severe neonatal-onset encephalopathy with microcephaly — 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 moduleSevere neonatal-onset encephalopathy with microcephaly 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 severe neonatal-onset encephalopathy with microcephaly 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
methyl-CpG binding protein 2 (MECP2) — MECP2 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6OGK · 1.65 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 157 full-term infants with neurological abnormalities in the first 48 hours after delivery, those with an Apgar score of 3 or below were the only ones who developed severe or moderate basal ganglia and thalamic lesions on MRI. Minimal basal ganglia and thalamic lesions were almost always associated with Apgar scores below 7. However, 28% of infants with Apgar scores below 3 had normal scans or only minimal white matter changes. White matter lesions without basal ganglia involvement occurred equally across all Apgar score groups. Cerebral infarction and scattered white matter haemorrhages were most common in infants with Apgar scores of 4 and above. The Apgar score was not always predictive of motor outcome at two years; outcome mainly reflected the site and severity of MRI findings.
Microcephaly can be present at birth or develop postnatally. In large cohorts, genetic factors and perinatal brain damage from maternal exposures and prenatally acquired infections are the leading causes, but in up to about 40% of children no cause is identified. Neuroimaging has the highest diagnostic yield in all-comers with microcephaly, with MRI providing the highest sensitivity. Genetic testing has the next highest yield; if no specific disorder is suspected, comparative genomic hybridisation is the recommended first-line genetic test. Definitive treatment for microcephaly does not exist. Supportive treatment aimed at preventing further damage or mitigating existing comorbidities may be available. Overall prognosis relates to severity of disease, underlying diagnosis, and comorbid conditions.
Most encephalopathies due to an underlying metabolic disorder are genetic, present early in life, and disrupt normal metabolic function. These disorders are individually rare but collectively common and are an important cause of preventable morbidity and mortality, both of which are high if the condition is missed or not treated early. There are more than 500 biochemically diverse disorders. The neonatal period is a time of substantial catabolism, and neonates have a limited response to severe overwhelming illness, resulting in death or permanent neurological sequelae.
What is still missing is a definitive treatment for microcephaly itself, and for the metabolic encephalopathies early diagnosis depends on specialised units that may not be universally available. The 2002 study did not address genetic or metabolic causes, and the 2017 primer notes that in about 40% of microcephaly cases no aetiology is identified, meaning a large fraction of patients remain without a clear target for intervention. No trial has tested a repurposed drug in this specific population of severe neonatal-onset encephalopathy with microcephaly.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuropediatrics · 2002 · 47 citations
MRI Lesions and Infants with Neonatal Encephalopathy. Is the Apgar Score Predictive?
AbstractOBJECTIVE: The aim of this study was to establish whether, in full-term infants presenting with neonatal encephalopathy, the 1 minute Apgar score gives an indication of the presence, site or type of lesions observed on brain MRI in the neonatal period. PARTICIPANTS AND METHODS: The study cohort included 157 full-term infants who had neurological abnormalities during the first 48 hours after delivery. Infants with developmental, genetic, infective or metabolic diagnoses were excluded from the study. The infants were subdivided according to their 1 minute Apgar score into three groups as follows: Apgar score 0 - 3 (n = 108/157, 69 %), 4 - 7 (n = 29, 19 %), 8 - 10 (n = 21, 12 %). Results. Severe and moderate basal ganglia and thalamic (BGT) lesions, with one exception, were only observed in the group with an Apgar score of 3 or below. Minimal BGT lesions were, with one exception, associated with scores below 7 and mainly below 3. However, not all the infants with low Apgar scores had BGT lesions and 28 % of the patients with Apgar scores below 3 had normal scans or only minimal white matter changes. White matter lesions without BGT involvement were equally distributed in the cohort, irrespective of the Apgar scores. Cerebral infarction and scattered white matter haemorrhages were the most common findings in infants with Apgar scores of 4 and above. The Apgar scores were not always predictive of motor outcome at 2 years but the presence and severity of the sequelae mainly reflected the site and severity of MRI findings. CONCLUSIONS: These findings stress the importance of subdividing neonatal encephalopathy into diagnostic categories according to brain lesions if one wishes to study either causative factors or outcome.
AbstractMicrocephaly can present in the newborn period, either at birth or postnatally. In large cohorts, genetic factors and perinatal brain damage secondary to maternal exposures and prenatally acquired infections are the leading causative factors. However, in up to ∼40% of children with microcephaly, no etiology is identified. Although many classifications exist, it is important to remember that both congenital microcephaly and postnatal-onset microcephaly can be due to genetic or “acquired” causes. Careful history and physical examination is the initial step in evaluating a neonate with microcephaly. Diagnostic evaluation should be tailored based on these findings. In all-comers with microcephaly, neuroimaging proves to have the highest diagnostic yield, with magnetic resonance imaging providing the highest sensitivity. Genetic testing has the next highest diagnostic yield, and if presentation does not suggest a specific genetic disorder, comparative genomic hybridization would be the recommended first-line genetic testing. Definitive treatment for microcephaly does not exist, but supportive treatment aimed at preventing further damage or mitigating untoward effects of existing comorbidities may be available. Overall prognosis relates to severity of disease, underlying diagnosis, and comorbid conditions identified. Zika virus is emerging as an infectious pathogen leading to congenital microcephaly. Given its potentially devastating effects, a low threshold of suspicion is warranted at this time for women presenting with a fever and rash during pregnancy with a personal history or sexual contact with a person who has a history of travel to affected regions, or with findings of microcephaly on prenatal ultrasonography.
AbstractMost encephalopaties due to an underlying metabolic (inborn error of metabolism) disorders are genetic, present early in life, and disrupt normal metabolic function. Most these disorders are individually rare, but collectively are common and important cause of preventable morbidity and mortality, both are high if missed or not treated early. There are more than 500 biochemically diverse disorders with many significant recent advances in the diagnosis and treatment that substantially improved prognosis. Pediatricians and neonatologists are vital in early identification, particularly given that the diagnosis needs to be established quickly. Collaboration with a specialized unit is needed for timely consultations and referrals. The neonatal period is a time of substantial catabolism, therefore, neonates has limited response to severe overwhelming illness resulting in death or permanent neurological sequelae. The aim of this chapter is to provide a practical approach to the recognition and investigations of metabolic encephalopathy presenting early in life. Guidelines for the stabilization and initial management will be provided.
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.
