DeCure for Microcephaly 19, primary, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for microcephaly 19, 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 19, 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 19, 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
coat protein complex I subunit beta 2 (COPB2) — COPB2 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 1r,2r,3s,4sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8D41 · 2.0 Å · ligand (1R,2R,3S,4S)-3-[4-(4-fluorophenyl)piperazine-1-carbonyl]bicyclo[2.2.1]heptane-2-carboxylic acid (Q93). Experimental structure, not a prediction.
What the evidence adds up to
A 1988 report describes a large family with 13 affected members across three generations showing autosomal dominant isolated microcephaly, with incomplete penetrance and a skipped generation. This uncomplicated type, without other dysmorphic or neurological abnormalities, is distinguished from other dominantly inherited forms. In contrast, a 1995 report describes five siblings in one family with autosomal recessive microcephaly accompanied by intractable seizures, quadriplegia, and profound mental retardation, noting that the recurrence risk may be high when such severe neurological deficits are present.
A 2010 study reports the unexpected finding of three different nonsense mutations in two unrelated individuals diagnosed with autosomal recessive primary microcephaly. In each case, one phenotypically normal parent carried two of the mutations, presumably in cis. This finding of triple pathogenic mutations has unknown incidence but significant implications for genetic counselling, as failing to detect all three could cause false positive or false negative diagnoses in other family members; genotyping the parents is recommended to avoid this.
A 2014 case report describes a reduced-intensity conditioning umbilical cord blood transplantation in a 19-month-old female child with Nijmegen breakage syndrome (NBS), a rare autosomal recessive disorder caused by NBN gene mutation that includes microcephaly, growth retardation, combined immunodeficiency, and strong predisposition to lymphatic malignancies. The report states there is no specific treatment for NBS and prognosis is generally poor, but presents this as a case of safe and successful non-myeloablative UCB transplantation in a patient with NBS concomitant with SCID.
A 2019 review notes that at least 25 genes (MCPH1-25) have been discovered to cause autosomal recessive primary microcephaly (MCPH) when mutated, characterised by decreased brain size, mental retardation, and abnormal behaviours. The review covers expression patterns, cellular localisation, molecular functions, and animal models of these proteins, but does not report any therapeutic trials or clinical interventions for MCPH. What remains missing is any clinical trial data for drug treatments in primary microcephaly, adequate patient stratification by specific MCPH gene mutation, and funding for preclinical or clinical studies targeting the underlying molecular pathways.
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 Medical Genetics · 1988 · 13 citations · open access
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.
Pediatric Transplantation · 2014 · 7 citations · open access
Reduced‐intensity conditioning umbilical cord blood transplantation in <scp>N</scp>ijmegen breakage syndrome
AbstractNBS is a rare autosomal recessive congenital disorder associated with chromosome instability caused by a mutation in the NBN gene (8q21). Clinical manifestations include microcephaly, growth retardation, combined immunodeficiency, and a strong predisposition to develop (mainly lymphatic) malignancies. There is no specific treatment for patients with NBS, and the prognosis is generally poor. The therapeutic option for some patients with NBS may be HSCT. We present a case of safe and successful non-myeloablative UCB transplantation in the 19th month of the life of a female child with NBS concomitant with SCID.
[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.
Critical consequences of finding three pathogenic mutations in an individual with recessive disease
AbstractThe authors report the unexpected finding of three different nonsense mutations in two unrelated individuals with a diagnosis of autosomal recessive primary microcephaly. In each case one phenotypically normal parent was found to carry two of the nonsense mutations, presumably in cis. This finding of 'triple pathogenic mutations' is of unknown incidence but has significant implication for genetic counselling. A failure to detect all three mutations could result in both false positive and false negative diagnoses in other family members. Both of these potential problems can be avoided by always genotyping the parents.
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.
