DeCure for Microcephaly 29, primary, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for microcephaly 29, 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 29, 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 29, 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
programmed cell death 6 interacting protein (PDCD6IP) — PDCD6IP 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 2XS1 · 2.296 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, expressive speech disorder, and epilepsy. The majority of known causative genes encode proteins implicated in cell division, many localised at the centrosome. Mutations in KIF14, encoding a kinesin-like protein, cause both primary and syndromic microcephaly, the latter adding growth retardation, renal and cranio-facial abnormalities. Despite more than ten genes reported to cause MCPH, many patients remain without a molecular diagnosis.
A 2020 report identified a novel compound heterozygous mutation in the STIL gene (c.2344_2347delTTGC, p.Leu782Thrfs*2; c.3838C>T, p.Arg1280Cys) in two consecutive microcephaly fetuses from a normal Chinese couple. Ultrasound and MRI showed both fetuses had a thick skull plate, unclear anterior horn of the lateral ventricle, and typical microcephaly. In one fetus, the fourth ventricle was dilated and the cerebellar vermis ascended. These findings extend the mutational and clinical spectrum of MCPH7 but offer no therapeutic intervention.
No drug treatment, clinical trial, or repurposing candidate is mentioned in any of these abstracts. The literature remains descriptive, focused on genetic diagnosis and counselling. What is missing is any preclinical model for drug screening, any funding for therapeutic development, and any stratification of patients by specific gene mutation that might guide a targeted approach.
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.
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.
Ultrasound in Obstetrics and Gynecology · 2020 · 0 citations · open access
VP25.09: A novel compound heterozygous mutation in STIL gene identified in a Chinese family with presentation of fetal microcephaly
AbstractPrimary microcephaly 7 (MCPH7) is an autosomal recessive human neurodevelopmental discorder featured with microcephaly, sloping forehead and prominent midface. STIL gene encodes a protein which regulates the mitotic spindle checkpoint. STIL is the pathogenetic gene of MCPH7. Although more than 10 genes have been reported to cause MCPH, many patients remain without a molecular diagnosis. The clinical manifestations and genetic factors of MCPH7 remain to be revealed. We report that a normal couple had two consecutive microcephaly fetuses. Ultrasound examination was conducted using Siemens S2000 colour Doppler ultrasound instrument phase array abdomen 6C2. Whole-genome sequencing (WGS) was conducted using fetal umbilical cord tissue and Sanger sequence was confirmed on parents. Prenatal and Postnatal MRI was conducted on the pregnant and the fetuses. Ultrasound examination showed the two fetuses suffered primary microcephaly. Using whole-genome sequencing, a novel compounds heterozygous mutation in STIL (c.2344_2347delTTGC, p.Leu782Thrfs*2; c.3838C>T, p.Arg1280Cys) were identified in two fetuses with MCPH7. The MRI results were quite similar. Postnatal MRI confirmed the ultrasound and prenatal examinations. The two fetuses had the typical symptoms of microcephaly. Ultrasound and MRI showed the two fetuses had thick skull plate. In II:2, the fourth ventricle dilated, cerebellum vermis ascended. Both fetuses had unclear anterior horn of lateral ventricle. Our findings have important implications on prenatal diagnosis and genetic counselling for any case with MCPH7. We extend both mutational spectrum in STIL gene and clinical spectrum of MCPH7. Supporting information can be found in the online version of this abstract Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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.
