DeCure for Cerebellar dysfunction with variable cognitive and behavioral abnormalities
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cerebellar dysfunction with variable cognitive and behavioral abnormalities — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCerebellar dysfunction with variable cognitive and behavioral abnormalities maps to a 6-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
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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 cerebellar dysfunction with variable cognitive and behavioral abnormalities 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
SET and MYND domain containing 3 (SMYD3) — SMYD3 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 samdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6P7Z · 1.19 Å · ligand S-ADENOSYLMETHIONINE (SAM). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective case series of 24 young adults (aged 18–44) with isolated infratentorial infarcts, 18 had cerebellar infarcts. Neurologic outcome was favourable in 22 patients according to the modified Rankin scale (grade 0–2) and the NIH stroke scale, yet 12 patients were on full or partial sick leave at 4 months and 10 at 12 months. Patients performed worse than controls on tasks of working memory, temporary storage of complex information, and cognitive flexibility. Verbal IQ (r = −0.74) and performance IQ (r = −0.78) correlated with infarct size. Block design performance early after stroke predicted maximal working capacity at 12 months. The authors concluded that cerebellar damage impairs attention and visuospatial skills, while intelligence and episodic memory remain unchanged unless large portions of the cerebellar hemispheres are involved.
A 61-year-old man with cerebellar haemorrhage presented with disorientation, recent memory disturbance, impaired attention, executive dysfunction, and reduced volition, alongside trunk and extremity ataxia but no paralysis or sensory loss. After exercise therapy, cognitive rehabilitation, and home modification, he could live at home under family supervision, but memory disturbance, attention disturbance, and executive impairment remained. The authors noted that cognitive dysfunction after cerebellar damage is assumed to arise from disruption of the cerebrocerebellar circuit, and that rehabilitation must include detailed assessment of cerebral function.
A 2005 review states that understanding of the cerebellum’s contribution to neurocognition is still nascent, partly because the cerebellum acts as a subtle modulator of neurocognitive processes, and deficits from its impairment are quantitatively and qualitatively different from those caused by supratentorial lesions. A 2019 article on Type 1 Chiari malformation raises the need for critical analysis of cognitive profiles in these patients and highlights problems that hinder the study of cognitive dysfunction in that population.
No drug or intervention was tested in any of these studies. What is missing is a systematic, prospective trial that stratifies patients by lesion location and size, uses standardised cognitive batteries at fixed time points, and includes a control group. Funding for such a trial, and for the development of rehabilitation protocols that address the specific cognitive profile of cerebellar cognitive affective syndrome, remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 1998 · 188 citations
Cognitive impairment in young adults with infratentorial infarcts
AbstractOBJECTIVE: To describe cognitive functions and functional outcome in young patients with isolated infratentorial infarcts. BACKGROUND: Contemporary knowledge implies a cerebellar contribution to cognitive behavior. Neuropsychological examination of patients with selective cerebellar lesions provides an opportunity to document the existence and nature of clinically relevant cognitive manifestations from lesions of the cerebellum. METHODS: Prospective case series. The patients were assessed acutely and at 4 and 12 months after onset. Twenty-four patients from a consecutive series of 105 patients aged 18 to 44 years with cerebral infarction had a brain stem or cerebellar infarction. Fourteen age-matched controls were used for neuropsychological comparisons. Evaluation included MRI, angiography, and transesophageal echocardiography. Disability and neurologic dysfunction were assessed by the modified Rankin scale, NIH stroke scale, and maximal working capacity. A comprehensive neuropsychological battery was performed at baseline in 20 of the 24 patients. RESULTS: Eighteen patients had a cerebellar infarct. Two patients had lateral medullary infarcts, and two isolated pontine infarcts. Twenty-two patients had a favorable outcome according to the modified Rankin scale (grade 0-2) and the NIH scale. In contrast, 12 patients were granted full or partial sick leave at the 4 months follow-up, and 10 patients at 12 months. Patients generally performed worse than controls in various aspects of cognitive function, especially in tasks concerning working memory, the temporary storage of complex information, and cognitive flexibility. Measures of verbal IQ (r = -0.74) and performance IQ (r = -0.78) were related to the size of the infarct. The block design task performance in the early poststroke period predicted maximal working capacity at 12 months. CONCLUSIONS: Cerebellar damage impairs central aspects of attention and visuospatial skills. In contrast, intelligence and episodic memory remain unchanged. When the lesion involves large portions of the cerebellar hemispheres, changes concerning broad areas of intelligence may occur. The prognosis is favorable for neurologic dysfunction, but cognitive deficits may prevent return to work.
Stroke rehabilitation in a patient with cerebellar cognitive affective syndrome
AbstractOBJECTIVE: It has become evident that the cerebellum plays a role in cognitive function, and Schmahmann et al. have introduced the term "Cerebellar cognitive affective syndrome (CCAS)." In the present paper we report a patient with cerebellar hemorrhage who developed CCAS. DESIGN: A case study. METHODS: The patient was a 61-year-old right-handed man who was admitted to our hospital because of sudden headache, dizziness and vomiting. The patient showed ataxia of the trunk and the extremities, but no paralysis and disturbance of sensation. He was disoriented in time and showed recent memory disturbance, disturbance of attention, impairment of executive functions and reduced volition, and due to these symptoms, his daily living was also severely impaired. RESULTS: With the aim of returning home, the patient received exercise therapy and cognitive rehabilitation, while home modification was performed, and living at home under the supervision of his family became possible. Cognitive function improved, while memory and attention disturbance, impairment of executive function remained. CONCLUSION: Cognitive dysfunction in patients with cerebellar damage is assumed to develop from disturbance of the cerebrocerebellar circuit, and that rehabilitation of these patients must include assessment of not only the motor function, but also of detailed assessment of cerebral function.
AbstractOur understanding of the contribution of the cerebellum to neurocognition is still in a nascent stage, essentially because of the historical negligence of the nonmotor role of the cerebellum. But it is also because the cerebellum acts primarily as a rather subtle modulator of neurocognitive processes. If this modulating function is impaired, deficits arise that are quantitatively and qualitatively different from the deficits produced by lesions of the supratentorial structures. This article reviews in further detail the current understanding of cognitive deficits associated with cerebellar impairments and unravels its modulating role in cognitive and behavioral processes.
Type 1 Chiari malformation and cognitive impairment: focus on the cerebellum
AbstractGiven evidence that cerebellar symptom in MK 1 is not limited to existing ideas. The role of the cerebellum in the control of not only motor but also cognitive functions is considered. The theory of universal cerebellar transformation (UCT) as a mechanism of complex regulation of motor and non-motor functions is discussed. The question is raised about the need for a critical analysis of the cognitive profile of patients with MK 1. The problems that lie in the way of studying cognitive dysfunction in patients with MK 1 are highlighted.
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.
