DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for corticobasal syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCorticobasal syndrome maps to a 3-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 corticobasal syndrome 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
TANK binding kinase 1 (TBK1) — TBK1 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 5-cyclopropyl-2-{[3-(morpholin-4-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4IM0 · 2.4001 Å · ligand N-{3-[(5-cyclopropyl-2-{[3-(morpholin-4-ylmethyl)phenyl]amino}pyrimidin-4-yl)amino]propyl}cyclobutanecarboxamide (1FV). Experimental structure, not a prediction.
What the evidence adds up to
A 2009 study of 21 patients from a single Basque lineage carrying the same PGRN splicing mutation (c.709-1G>A) found that corticobasal syndrome emerged as a secondary or tertiary diagnosis in 47.6% of cases, typically about two years after the initial presentation. The most common presenting syndromes were behavioural variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%). At initial assessment, 81.8% of these patients already showed neuropsychological features of parietal lobe dysfunction. The authors concluded that patients with this mutation commonly develop corticobasal syndrome as the disease progresses.
A 2021 systematic review of genetically confirmed corticobasal syndrome cases identified 58 eligible patients from 40 publications published between 1999 and 2020. GRN was the most common gene involved, accounting for 28 of the 58 cases, followed by MAPT, C9ORF72, and PRNP. Among GRN-related corticobasal syndrome patients, a set of symptoms was significantly more common: visuospatial impairment, behavioural changes, aphasia, and language alterations. The review also examined eight additional articles on genetic risk factors for corticobasal syndrome. The authors proposed a diagnostic algorithm to help identify potential genetic cases, but no treatment or intervention was tested or recommended.
A 2021 case report describes a patient clinically diagnosed with corticobasal syndrome whose initial presentation was psychiatric: psychotic depression and delusional jealousy. The authors note that misdiagnosing these psychiatric presentations may delay treatment initiation and worsen the patient's condition, and that COVID-19-related changes in health service organisation complicated diagnosis and follow-up for this single patient. A 2017 review characterises corticobasal syndrome as a clinically and pathologically heterogeneous condition marked most often by asymmetric parkinsonism and apraxia, with or without cognitive dysfunction, and discusses how genetic and neuropathologic factors interact with vulnerable brain regions to produce symptoms.
What is still missing are large, prospective, genetically stratified natural history studies that can reliably link specific mutations to clinical trajectories, and any controlled trial testing a disease-modifying intervention in corticobasal syndrome. The existing evidence is limited to small case series, retrospective reviews, and single case reports. No therapy has been shown to slow progression or improve outcomes in this population.
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 · 2009 · 37 citations
“Frontotemporoparietal” dementia
AbstractBACKGROUND: Mutations in the progranulin gene (PGRN) are a major cause of frontotemporal lobar degeneration with tau-negative and ubiquitin-positive neuronal inclusions. Most previous studies aimed at characterizing the clinical and neuropsychological phenotype of PGRN mutation carriers included patients with different PGRN mutations, assuming that the common proposed pathogenetic mechanism of haploinsufficiency will lead to a comparable phenotype. METHODS: We studied 21 patients with a single pathogenic splicing mutation in the PGRN gene (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic criteria and protocols. All patients were of Basque descent. RESULTS: Patients exhibited a variable phenotype both in age at onset and initial symptoms. Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%) were the most common presenting syndromes. Apathy was the most common behavioral symptom. Patients developed a relatively rapidly progressive dementia with features that led to a secondary diagnosis in 61.9% of cases 2 years after primary diagnosis. Notably, this secondary or tertiary diagnosis was corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological features of parietal lobe dysfunction seen at the initial assessment in 81.8% of patients. CONCLUSIONS: Patients carrying the c.709-1G>A mutation in the PGRN gene showed heterogeneous clinical and neuropsychological features and commonly developed corticobasal syndrome as the disease progressed.
Unravelling Genetic Factors Underlying Corticobasal Syndrome: A Systematic Review
AbstractCorticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS cases are sporadic; nevertheless, reports of families and isolated individuals with genetically determined CBS have been reported. In this systematic review, we analyze the demographical, clinical, radiological, and anatomopathological features of genetically confirmed cases of CBS. A systematic search was performed using the PubMed, EMBASE, and Cochrane Library databases, included all publications in English from 1 January 1999 through 1 August 2020. We found forty publications with fifty-eight eligible cases. A second search for publications dealing with genetic risk factors for CBS led to the review of eight additional articles. GRN was the most common gene involved in CBS, representing 28 out of 58 cases, followed by MAPT, C9ORF72, and PRNP. A set of symptoms was shown to be significantly more common in GRN-CBS patients, including visuospatial impairment, behavioral changes, aphasia, and language alterations. In addition, specific demographical, clinical, biochemical, and radiological features may suggest mutations in other genes. We suggest a diagnostic algorithm to help in identifying potential genetic cases of CBS in order to improve the diagnostic accuracy and to better understand the still poorly defined underlying pathogenetic process.
An atypical case of corticobasal syndrome with psychotic depression and delusional jealousy
AbstractCorticobasal syndrome (CBS) is one of the Parkinson-plus disorders. While initially defined as a movement disorder rather than cognition, it is now known that CBS is related to various psychiatric symptoms. We describe a patient clinically diagnosed with CBS whose initial presentation was psychiatric and rather atypical. His clinical picture included psychotic depression and delusional jealousy. Misdiagnosing these syndromes may delay the initiation of the treatment and worsen the patients' condition, as well as increase the burden of the caretakers. Finally, COVID-19-related changes in the organization of health services complicated the diagnosis and follow-up processes of this patient.
Oxford University Press eBooks · 2017 · 0 citations
Parkinson Syndromes
AbstractCorticobasal syndrome (CBS) is a clinically and pathologically heterogenous condition marked most often by asymmetric parkinsonism and apraxia, with or without cognitive dysfunction. This review considers the genetic and neuropathologic origins of the syndrome, and discusses how these factors interact with the anatomy and function of vulnerable brain regions to produce the distinct set of symptoms characteristic of CBS. It also discusses how these observations affect the rationale and development of therapies for CBS and other neurodegenerative 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.
