DeCure for Isolated cerebellar hypoplasia/agenesis
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for isolated cerebellar hypoplasia/agenesis — screening already-approved drugs against its 39-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIsolated cerebellar hypoplasia/agenesis maps to a 39-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 isolated cerebellar hypoplasia/agenesis 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
calcium/calmodulin dependent serine protein kinase (CASK) — CASK 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 2r,3s,4r,5rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3C0I · 1.85 Å · ligand [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate (3AM). Experimental structure, not a prediction.
What the evidence adds up to
Isolated cerebellar hypoplasia or agenesis is a rare condition. A 1999 report described two families with diffuse pachygyria and cerebellar hypoplasia whose CT and MRI showed decreased gyral formation and marked cerebellar hypoplasia; the authors considered this a possible new autosomal recessive syndrome distinct from microlissencephaly because no polymicrogyria was seen and clinical findings were milder. A 2002 paper stated that total or subtotal cerebellar agenesis is very rare and that the case presented was, to the authors' knowledge, only the sixth living case in the literature. A 2009 study of a patient with partial cerebellar agenesis reported only mild cerebellar signs on neurological exam but severe deficits on neuropsychological testing; fMRI showed activation and symmetrical perfusion of cerebellar remnants, while SPECT revealed left frontal and parieto-temporal cortex hypoperfusion that the authors linked to the severe cognitive impairment. A 2024 case report described an 11-month-old with developmental delay whose CT showed complete absence of the cerebellum with no other cerebral malformation.
No drug treatment is mentioned in any of these abstracts. A 2025 review of cerebellar development discusses BDNF/TrkB signalling as a pathway involved in cerebellar foliation and notes that hypoplasia of vermal lobules VI-VII has been linked to autism spectrum disorder. The review asks whether restoring BDNF signalling could reverse cerebellar developmental disorders, but this is a speculative question based on mouse genetic studies, not a tested intervention in humans.
The evidence consists entirely of case reports and a review. There are no clinical trials, no tested drugs, and no data on any intervention changing the course of cerebellar hypoplasia or agenesis. What is missing is any preclinical or clinical work that moves from describing the developmental signalling pathways to testing a specific molecule in patients, along with the funding and trial design needed to attempt such a study. Patient stratification by genetic cause and severity of cerebellar deficit would also be required before any therapy could be evaluated.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 1999 · 21 citations
Diffuse pachygyria with cerebellar hypoplasia: A milder form of microlissencephaly or a new genetic syndrome?
AbstractWe report on 2 families with diffuse pachygyria and cerebellar hypoplasia, who presented hypotonia, ataxia, seizures, and developmental delay since infancy. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed decreased gyral formation in the cerebral cortex and marked hypoplasia in the cerebellum. Cerebellar hypoplasia is often associated with type 2 lissencephaly; however, our cases showed no polymicrogyria, and their clinical findings were quite mild compared with those of microlissencephaly. Their characteristic phenotype suggested a new genetic syndrome, which was possibly inherited as an autosomal recessive trait.
Primary Cerebellar Agenesis – Chiari Iv Malformation
AbstractTotal or subtotal cerebellar agenesis that was described firstly by M. Combettes in 1831 is very rare. Severe dysfunction in movement is observed in the cerebellar lesions. Since there is a significant recovery in movement partial cerebellum lesions, it has been suggested that normal movement is not absolute dependent to cerebellum. But this issue is still controversial. The cases of complete cerebellar agenesis in the literature are usually reported in the autopsy. The study presented here is the sixth living case in the literature according to our knowledge.Primer Serebellar Agenezi - Chiari IV MalformasyonuTotal yada subtotal serebellar ag enezi ilk kez 1831'de M.Combettes taralından tariftenen çok nadir bir durumdur. Serebellum lezyonlarmda hareketde ciddi bozukluk gözlenir. Parsiyel serebellum lezyonlarmda belirgin bir iyileşme olduğundan dolayı serebellumun normal hareket ile ilgili olmadığı düşünülür. Literatürdeki total serebellar agenezi vakaları genellikle otopsilerde bildirilmiştir. Burada sunulan vaka, literatürde bizim bildiğimiz yaşayan altıncı vakadır.
Neuropsychological and functional study in a case of partial cerebellar agenesis
AbstractCerebellar agenesis is a rare disorder. We present the neurological and neuropsychological features of a patient with partial cerebellar agenesis (TZ), together with SPECT perfusion and fMRI activation during a finger tapping task. TZ shows only mild cerebellar signs, while neuropsychological testing discloses severe deficits in many domains, in accordance with the theorized role of the cerebellum in cognition. FMRI and SPECT demonstrate an activation and a symmetrical perfusion of the cerebellar remnants, that can be related to the residual cerebellar motor function. The left frontal and parieto-temporal cortex hypoperfusion can explain the severe cognitive impairment and could be linked to the abnormal cerebellar development.
Radiology Case Reports · 2024 · 1 citations · open access
Total cerebellar agenesis: A case report of a very rare condition
AbstractComplete cerebellar agenesis is an extremely rare condition characterized by the complete absence of cerebellar tissue. Only a small number of cases have been reported, with varying motor and cognitive deficits. We describe a case of an 11-month-old baby with developmental delay, whose CT scan evaluation showed the complete absence of the cerebellum with no other associated cerebral malformation.
Frontiers in Cellular Neuroscience · 2025 · 0 citations · open access
Sculptors of cerebellar fissures and their potential as therapeutic targets for cerebellar dysfunction
AbstractThe cerebellum plays an important role in both motor control and cognition. The cerebellar cortex is neuron-rich and composed of characteristic folia and fissures. Defective cerebellar development leads to movement disorders and developmental delay. During early morphogenesis, cellular signaling programs orchestrate simultaneous cerebellar growth and foliation. Aberrant signaling causes various degrees of cerebellar hypoplasia. Based on mouse genetic studies, we discuss several developmental signaling pathways that drive cerebellar morphogenesis. Notably, hypoplasia of vermal lobules VI-VII has been linked to autism spectrum disorder and is in part attributed to brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B signaling. This review also discusses how BDNF biogenesis is critical for cerebellar foliation and whether restoring BDNF signaling could reverse cerebellar developmental disorders.
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.
