DeCure for Microcephaly 27, primary, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for microcephaly 27, primary, autosomal dominant — 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 27, primary, autosomal dominant 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 27, primary, autosomal dominant 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.
What the evidence adds up to
A 1981 report describes a family with microcephaly observed across at least three generations, consistent with autosomal dominant inheritance. Affected individuals also had significantly short stature, ocular anomalies, and simple, protruding ears, but intellectual function was in the normal or borderline range. No other abstracts address autosomal dominant microcephaly; the remaining abstracts concern autosomal recessive primary microcephaly (MCPH), a genetically and clinically distinct disorder.
Autosomal recessive primary microcephaly is a neurogenic mitotic disorder characterised by decreased brain size and mental retardation. By 2020, 25 genes (MCPH1–25) had been identified. The inactivation of most MCPH genes leads to neurogenesis defects, while upregulation of some is associated with carcinogenesis. A 2019 review summarised the expression patterns, cellular localisation, molecular functions, and animal models of these 25 proteins. A 2008 neuropathologic study noted that MCPH patients have a significantly reduced occipito-frontal head circumference (more than three standard deviations below the mean) and reduced brain volume, especially of the cerebral cortex, with simplified cortical structure and slightly reduced white matter. Cytoarchitectonic anomalies, predominantly in the first two cortical layers, included compact cell clusters in the second layer, suggesting proliferation/differentiation or migration defects. No myelination disturbances were observed.
No drug, treatment, or intervention is mentioned in any of these abstracts. The autosomal dominant form described in 1981 appears to have a milder cognitive outcome than autosomal recessive MCPH, but no molecular or genetic data for the dominant form are provided beyond the pedigree. What is still missing is any genetic characterisation of the dominant form, any animal model for it, any systematic neuropathology, and any clinical trial or therapeutic strategy for either form.
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 · 1983 · 26 citations
Silent microcephaly: A distinct autosomal dominant trait
AbstractThirteen patients from three unrelated families were found to have microcephaly, without any neurological or dysmorphic manifestations. Autosomal dominant inheritance is concluded since the trait was transmitted directly in all three families, including one male-to-male instance. The recognition of this uncomplicated form of microcephaly as a Mendelian trait further extends its etiological heterogeneity.
Dominant inheritance of microcephaly with short stature
AbstractA family is reported in which microcephaly has been observed in at least three generations. The pedigree is most consistent with autosomal dominant inheritance. In addition to microcephaly, affected individuals exhibit significantly short stature, ocular anomalies and simple, protruding ears. Intellectual function is in the normal or borderline range.
International Journal of Molecular Sciences · 2020 · 19 citations · open access
The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis
AbstractThe stem cells of neurogenesis and carcinogenesis share many properties, including proliferative rate, an extensive replicative potential, the potential to generate different cell types of a given tissue, and an ability to independently migrate to a damaged area. This is also evidenced by the common molecular principles regulating key processes associated with cell division and apoptosis. Autosomal recessive primary microcephaly (MCPH) is a neurogenic mitotic disorder that is characterized by decreased brain size and mental retardation. Until now, a total of 25 genes have been identified that are known to be associated with MCPH. The inactivation (yin) of most MCPH genes leads to neurogenesis defects, while the upregulation (yang) of some MCPH genes is associated with different kinds of carcinogenesis. Here, we try to summarize the roles of MCPH genes in these two diseases and explore the underlying mechanisms, which will help us to explore new, attractive approaches to targeting tumor cells that are resistant to the current therapies.
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.
[Update on autosomal recessive primary microcephaly (MCPH)-associated proteins].
AbstractBrain development diseases refer to a group of diseases that affect the development of the brain or the central nervous system. Autosomal recessive primary microcephaly (MCPH) is a typical neurodevelopmental disorder characterized by a decreased brain size, mental retardation and abnormal behaviors. To date, at least 25 genes have been discovered to cause MCPH when mutated. These genes were named MCPH1-25 according to the discovery order. MCPH proteins play important roles in regulating brain developmental signaling pathways. Here, we provide a timely review of the expression patterns, cellular localization, molecular functions, phenotypes, as well as animal models of these 25 MCPH proteins that will expedite our understanding of the pathogenesis of brain disorders at both molecular and cellular levels.
Neuropathologic findings in patients with primary autosomal recessive microcephaly
AbstractAutosomal recessive primary microcephaly (MCPH, syn. Microcephalia vera) is a rare, genetically heterogeneous disease, in which patients exhibit microcephaly by the 32nd week of gestation. Genetic causes of MCPH subtypes 1–6 include mutations in genes encoding microcephalin (MCPH1), cyclin dependent kinase 5 regulatory associated protein 2 CDK5RAP2 (MCPH3), abnormal spindle-like, microcephaly associated ASPM (MCPH5), centromeric protein J CENPJ (MCPH6) as well as linkage to the two loci 19q13.1–13.2 (MCPH2) and 15q15-q21 (MCPH4). Severe microcephaly is characterized by a significantly reduced occipito-frontal head circumference (OCF) of more than three standard deviations below the mean for age, sex, and ethnicity. Microcephaly correlates closely with reduced brain volume and mental retardation, but patients with MCPH typically do not have further neurological findings. Imaging studies show brains of normal architecture but of reduced size. The latter is particularly evident in the cerebral cortex, which shows a simplified cerebral cortex structure, and there is also a slightly reduced white matter volume. Individual patients with MCPH provide evidence of periventricular neuronal heterotopias suggesting neuronal migration defects. It is not known whether the brain pathology in patients with MCPH is the result of defective cell proliferation/differentiation, cell migration and/or increased cell death. Neuropathological studies, which are rare and were performed at a time when a genetic diagnosis could not be performed, are thus highly warranted. Here, we summarize current knowledge on histological findings in MCPH patients. Infants with Microcephalia vera exhibited a significantly reduced brain volume with an almost preserved convolution pattern and no myelination disturbances. Cytoarchitectonic anomalies, seen predominantly in the first two cortical layers, included the appearance of compact cell clusters in the second layer. This can be interpreted as being indicative of a proliferation/differentiation and/or migration defect.
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.
