DeCure for Microcephaly 22, primary, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for microcephaly 22, primary, autosomal recessive — 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 22, primary, autosomal recessive 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 22, primary, autosomal recessive 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
non-SMC condensin II complex subunit D3 (NCAPD3) — NCAPD3 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 9F5W · 7.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Autosomal recessive primary microcephaly (MCPH) is a genetically heterogeneous neurodevelopmental disorder defined by a significantly reduced head circumference at birth and intellectual disability. Inconsistent features include hyperactivity, an expressive speech disorder, and epilepsy. The majority of known genes implicated in MCPH encode proteins that localise to the centrosome and are involved in cell division. Mutations in CDK5RAP2 cause MCPH, characterised by a pronounced reduction of brain volume, particularly of the cerebral cortex. Mutations in KIF14 cause both primary and syndromic microcephaly, the latter including growth retardation, renal and cranio-facial abnormalities. Mutations in MCPH1, encoding microcephalin, cause primary microcephaly associated with premature chromosome condensation; microcephalin contains BRCT domains and has roles in cell cycle, chromosome condensation and DNA repair. In one PhD project, a mouse model of impaired microcephalin function displayed misregulated chromosome condensation, and three mutations in the ASPM gene were identified for MCPH type five: p.Arg3096X, p.Arg1019X and the first reported missense variant p.Lys1862Gln.
Not all microcephaly follows autosomal recessive inheritance. One large family with 13 affected members in three generations showed autosomal dominant isolated microcephaly with incomplete penetrance, including a skipped generation and male-to-male transmission. This uncomplicated type should be distinguished from other dominantly inherited forms. In contrast, five siblings in one family with autosomal recessive microcephaly presented with marked microcephaly, intractable seizures, quadriplegia and profound mental retardation, deviating from the usual description of normal developmental milestones and minor neurological deficits. The recurrence risk in such families may be high, underscoring the importance of genetic counselling.
No drug treatments are mentioned in any of these abstracts. No clinical trials, no repurposing candidates, no survival or response rates are reported. The literature is entirely genetic and descriptive, focused on gene discovery, inheritance patterns and clinical characterisation.
What is missing is any pharmacological intervention, any preclinical model testing a drug, any trial design, any patient stratification beyond genetic diagnosis, and any funding directed at treatment development rather than gene identification.
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 · 2017 · 91 citations
Autosomal Recessive Primary Microcephaly (MCPH): An Update
AbstractAutosomal recessive primary microcephaly (MCPH; MicroCephaly Primary Hereditary) is a genetically heterogeneous neurodevelopmental disorder characterized by a significantly reduced head circumference present already at birth and intellectual disability. Inconsistent features include hyperactivity, an expressive speech disorder, and epilepsy. Here, we provide a brief overview on this rare disorder pertinent for clinicians.
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.
German Medical Science (German Research Foundation) · 2012 · 0 citations · open access
CDK5RAP2 expression during murine and human brain development correlates with pathology in primary autosomal recessive microcephaly
AbstractHomozygous mutations in the Cyclin dependent kinase 5 regulatory subunit-associated protein 2 geneCDK5RAP2cause primary autosomal recessive microcephaly (MCPH). MCPH is characterized by a pronounced reduction of brain volume, particularly of the cerebral cortex, and mental retardation. Though it is [for full text, please go to the a.m. URL]
Mutations in KIF14, Encoding Kinesin-Like Protein KIF14, Cause Primary and Syndromic Microcephaly
AbstractPrimary microcephaly (small head) is a neurodevelopmental disorder characterized by a reduction in the size of the cerebral cortex accompanied with mild to moderate intellectual disability. This condition is observed either as an isolated form referred to as autosomal recessive primary microcephaly (MCPH) or in combination with additional features like growth retardation, renal and cranio-facial abnormalities or others subsumed under syndromic microcephaly. Both MCPH and syndromic microcephaly are heterogeneous disorders caused by mutations of many different genes. The majority of these genes encode proteins implicated in cell division and many of them have been localized at the centrosome.
Refubium (Universitätsbibliothek der Freien Universität Berlin) · 2013 · 0 citations · open access
Molecular genetic and cytogenetic analyses of autosomal recessive primary microcephaly (MCPH)
AbstractAutosomal recessive primary microcephaly (MCPH) is a neurodevelopment disorder, arising from a failure in embryonic neurogenesis, leading to microcephaly at birth. All known genes implicated in this disorder are involved in the monitoring of centrosome integrity. Mutations in the human gene MCPH1, encoding microcephalin protein, cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC). Microcephalin contains highly conserved BRCT domains and has fundamental roles in cell cycle, chromosome condensation and DNA repair. The PhD project included generation of the first mouse model of impaired microcephalin function displaying the cellular phenotype of misregulated chromosome condensation, mapping a candidate MCPH locus on chromosome 10q11.23-21.3, reporting on a functionally notable MCPH1 missense mutation, p.Trp75Arg, with destabilizing effect on BRCT domain and identification of three mutations in the ASPM gene for MCPH disorder type five: p.Arg3096X, p.Arg1019X and the first reported missense variant p.Lys1862Gln. These results together provide further biological evidence for the MCPH proteins essential roles in brain development.
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.
