DeCure for Autosomal recessive primary microcephaly
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive primary microcephaly — screening already-approved drugs against its 29-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAutosomal recessive primary microcephaly maps to a 29-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 autosomal recessive primary 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
centromere protein E (CENPE) — CENPE 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8HFH · 1.8 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
The 2009 study of 21 Pakistani families with autosomal recessive primary microcephaly found that 18 families showed linkage to the MCPH5 locus on chromosome 1, which contains the ASPM gene. Sequence analysis of ASPM in those 18 families identified two novel nonsense mutations (c.2101C>T/p.Q701X and c.9492T>G/p.Y3164X) in two families and two novel deletion mutations (c.6686delGAAA/p.R2229TfsX9 and c.77delG/p.G26AfsX41) in two other families. Three previously described mutations (c.3978G>A/p.W1326X, c.1260delTCAAGTC/p.S420SfsX32, and c.9159delA/p.K3053NfsX4) were detected in 11 families. No drug or treatment was tested in this study.
A 1988 report described a large family with 13 affected members across three generations who had isolated microcephaly without other dysmorphic or neurological abnormalities. The pedigree showed autosomal dominant inheritance with incomplete penetrance, including one instance of male-to-male transmission and a non-manifesting heterozygote causing a skipped generation. The authors noted considerable variation in phenotypic expression and argued that this uncomplicated type should be distinguished from other dominantly inherited forms of microcephaly. No drug or treatment was tested.
A 1995 report described five siblings in one family with marked microcephaly, intractable seizures, quadriplegia, and profound mental retardation. The authors stated that autosomal recessive microcephaly is usually characterised by normal developmental milestones and minor neurological deficits, but this family presented with devastating neurological deficits and a high recurrence risk. The paper emphasised the importance of genetic counselling. No drug or treatment was tested.
No clinical trial data exist for any drug treatment in autosomal recessive primary microcephaly. What is missing is any preclinical or clinical work testing a pharmacological intervention, any attempt at patient stratification beyond genetic linkage, and any funding for a treatment development pipeline.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Child Neurology · 2009 · 23 citations
Mutation Analysis of the <i>ASPM</i> Gene in 18 Pakistani Families With Autosomal Recessive Primary Microcephaly
AbstractAutosomal recessive primary microcephaly (MCPH) is a rare neurological disorder, in which the patients exhibit reduced occipital frontal head circumference (>3 standard deviations) and mild-to-severe mental retardation. Autosomal recessive primary microcephaly is genetically heterogeneous and 7 loci have been reported to date. Mutations in ASPM (abnormal spindle-like, microcephaly associated) gene are the most common cause of autosomal recessive primary microcephaly in the majority of the reported families. In the current investigation, we have located and studied 21 families with autosomal recessive primary microcephaly. Genotyping using polymorphic microsatellite markers linked to 7 autosomal recessive primary microcephaly loci revealed linkage of 18 families to the MCPH5 locus. Sequence analysis of the ASPM gene in 18 linked families detected 2 novel nonsense mutations (c.2101C>T/p.Q701X; c.9492T>G/p.Y3164X) in 2 families and 2 novel deletion mutations (c.6686delGAAA/p.R2229TfsX9; c.77delG/p.G26AfsX41) in 2 other families. Three previously described mutations (c.3978G>A/p.W1326X; c.1260delTCAAGTC/p.S420SfsX32; c.9159delA/p.K3053NfsX4) were also detected in 11 families. These identified mutations extended the body of evidence implicating the ASPM gene in the pathogenesis of human hereditary primary microcephaly.
AbstractA large family (13 affected members in three generations) is reported in which isolated microcephaly occurred without any other dysmorphic or neurological abnormalities. The family pedigree confirms the autosomal dominant mode of inheritance with incomplete penetrance, including one example of male to male transmission and the occurrence of a non-manifesting heterozygote resulting in a 'skipped generation'. There is considerable variation in the phenotypic expression of autosomal dominant microcephaly. This isolated (uncomplicated) type of microcephaly should be distinguished from other well defined, dominantly inherited forms of microcephaly.
Familial microcephaly with severe neurological deficits: a description of five affected siblings
AbstractAutosomal recessive microcephaly is usually characterized by normal developmental milestones and minor neurological deficits. In this report, we describe five siblings in one family with marked microcephaly, intractable seizures, quadriplegia and profound mental retardation. The recurrence risk of microcephaly when associated with devastating neurological deficits, as exemplified by this family, may be high and in such cases, the role of appropriate genetic counseling is of utmost importance.
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.
