DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cerebral cavernous malformation — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCerebral cavernous malformation maps to a 5-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 cerebral cavernous malformation 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
KRIT1 ankyrin repeat containing (KRIT1) — KRIT1 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4HDO · 1.67 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Cerebral cavernous malformations are benign vascular anomalies of the central nervous system. Most patients are asymptomatic, but when symptoms occur they include epileptic seizures, focal neurological deficits, and headaches. The natural history is poorly defined. One series of 78 patients with brainstem cavernous malformations reported a prospective annual rehemorrhage rate of 33% per lesion per year; all those patients had associated venous malformations. In a separate series of 55 patients with brainstem cavernous malformations, all presented with haemorrhagic onset. After surgery, neurological status improved postoperatively in 34 cases at last follow-up, while five patients showed clinical neurological worsening. Total resection was achieved in 46 cases, and during a mean follow-up of 63.4 months no recurrence or re-bleeding occurred in those patients.
Surgical resection is the main intervention for symptomatic lesions causing neurologic deficits, seizures, or high risk of continued haemorrhage. In a review of 72 operated patients from a series of 78, 60 were the same or better after surgery. A separate report of six symptomatic patients managed over five years states that the best treatment for symptomatic cerebral cavernous malformation is microsurgical excision. Asymptomatic cavernomas need no treatment. The 2024 update notes that clinical management is challenging because decision-making must weigh the risk of cavernoma-related haemorrhage against the risks of surgical intervention and the natural course.
There are no disease-modifying drugs for cerebral cavernous malformations. A 2025 study describes the development of a proposed platform trial design, the Cavernous malformations A Randomised Efficacy MAster Protocol study, which would evaluate aspirin and propranolol as the first two interventions compared with standard care in a three-arm, two-stage multiarm multistage adaptive treatment selection randomised trial. The study identified 14 countries with clinical leadership and a funding agency that could support an international trial, and obtained one letter of collaboration from a commercial partner. A stage 1 proposal was submitted to the National Institute for Health and Care Research Efficacy and Mechanism Evaluation programme; a resubmission was encouraged but the committee required further justification for the choice of the intermediate phenotype used for treatment selection, biomarker validation work, and details about the pipeline of interventions.
What is still missing is a funded, recruiting platform trial that can test drug candidates in a randomised, controlled fashion. The proposed trial design exists but requires further biomarker validation, justification of the intermediate phenotype, and a clearer pipeline of candidate drugs before funding is secured. No drug has been shown in a randomised trial to alter the course of cerebral cavernous malformations in humans.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Asian Journal of Neurosurgery · 2019 · 19 citations · open access
Management and surgical approaches of brainstem cavernous malformations: Our experience and literature review
AbstractINTRODUCTION: Brainstem cavernous malformations (BSCMs) are clusters of dilated sinusoidal channels. Clinical presentation is characterized by focal neurological deficits and/or hemorrhage. The goal of this study is to analyze surgical indications and approaches in a series of patients with BSCM and review pertinent literature and suggest prognostic factors related to the anatomical, clinical, and surgical data collected. METHODS: We retrospectively reviewed the clinical data of 55 patients with BSCM, treated at three centers, from January 2006 to March 2016. We collected anagraphic data, pre and postoperative neurological status, pre and postradiological images, surgical procedures, and follow-up results. We summarized the anatomical, clinical, and surgical aspects of the lesions and identified two large groups based on the chosen approach: lateral and medial. Clinical and radiological results were then compared. RESULTS: The series comprised 55 patients. Hemorrhagic onset was observed in all patients. Suboccipital, retrosigmoid, anterior, subtentorial, subtemporal, transvermian, telovelar, far lateral and trans, and infratentorial approaches were performed. Neurological status improved postoperatively in 34 cases at last follow-up. Five patients showed clinical neurological worsening. Total resection was achieved in 46 cases and, during a mean follow-up of 63.4 months, no recurrence or re-bleeding occurred in those patients. The mean follow-up was 63.9 months. The mean modified Rankin Scale at final follow-up was used to analyze the results and draw our conclusions. CONCLUSIONS: A reasonable surgical approach, selection, and gentle handling of the surrounding structures are required to prevent impairment of neurologic function and avoid partial resection.
Journal of Personalized Medicine · 2022 · 7 citations · open access
Tailored Treatment Options for Cerebral Cavernous Malformations
AbstractThe diagnosis and treatment of cerebral cavernous malformations (CCMs), or cavernomas, continues to evolve as more data and treatment modalities become available. Intervention is necessary when a lesion causes symptomatic neurologic deficits, seizures, or has high risk of continued hemorrhage. Future medical treatment directions may specifically target the pathogenesis of these lesions. This review highlights the importance of individualized treatment plans based on specific CCM characteristics.
Surgical Approaches to Brain Stem Cavernous Malformations
AbstractIntroduction: Brain stem cavernous malformations are rare intracranial vascular lesions. They account for 9 to 35% of all cavernous malformations. Their natural history is poorly defined, and surgical series to date have been small. Methods: We reviewed our clinical experience from 1988 to 1996 with 78 patients with brain stem cavernous malformations and attempted to determine the hemorrhage rate and factors that influence outcome. There were 30 males and 48 females (mean age, 37 years). The lesions were located throughout the brain stem: the pons (27), pontomesencephalic (17), medulla (13), midbrain (11), pontomedullary function (8), and midbrain-pons-medulla (2). We also evaluated their neurological morbidity and mortality. Results: The prospective annual rehemorrhage rate was 33% per lesion per year. All patients had associated venous malformations. Standard skull base approaches were used to resect 72 of the 78 lesions. Of the 72 operated patients, 60 were the same or better after surgical...
[Clinical management of patients with cavernous malformations of the central nervous system: an update and recommendations for clinical practice].
AbstractINTRODUCTION: Cerebral cavernous malformations are benign vascular anomalies of the central nervous system (CNS). The clinical presentation of a cavernoma depends on its location. The majority of patients with cavernomas are asymptomatic. The most common symptoms include epileptic seizures, focal neurological deficits and/or headaches. The clinical management of cavernomas is challenging because numerous factors influence decision-making. These factors include the risk stratification of cavernoma-related hemorrhage, weighing the risks of surgical intervention against the natural course of the cavernoma and the clinical presentation. This article presents current guidelines and recommendations for clinical practice, based on the latest research findings and expert opinions. The article focuses on diagnostic approaches, risk stratification, therapeutic management and follow-up strategies.
Efficacy and Mechanism Evaluation · 2025 · 0 citations · open access
Developing a Randomised Efficacy PREcision medicine Platform trial design for Cavernomas: the CARE PREP study
AbstractBackground Symptomatic cerebral cavernous malformations are a rare sporadic or familial disease, which may cause haemorrhagic strokes or epileptic seizures. In 2015, a James Lind Alliance Priority Setting Partnership ranked targeted drug therapies as fourth of the top 10 research priorities for cerebral cavernous malformations. There are no disease-modifying drugs for cerebral cavernous malformations, but there are several promising candidates with proof of concept in human and animal studies. There are no platform trials for cerebral cavernous malformations. Objectives (1) Consolidate and initiate international collaborations between cerebral cavernous malformations researchers, cerebral cavernous malformations patient and public involvement groups, cerebral cavernous malformations research networks, and commercial partners; (2) Finalise a protocol for an efficient, international platform trial of multiple drugs using precision medicine (sporadic vs. familial cerebral cavernous malformations) that is both feasible and acceptable to patients and regulators; (3) Estimate the research, support and treatment costs of the platform trial and apply to the National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme. Methods A National Institute for Health and Care Research Efficacy and Mechanism Evaluation Application Acceleration Award funded this project from September 2022 to August 2023. A trial manager supported the Chief Investigator in growing and leading a multidisciplinary international collaboration, including a patient and public involvement advisory group, in a series of meetings to optimise study design, equality, diversity and inclusion. Edinburgh Innovations established connections with commercial partners with candidate drugs. We assessed feasibility by scoping potential funding agencies, and clinical networks that might support recruitment internationally. We agreed upon a final design and sample size through a process of consensus, enlightened by scenarios simulated by statisticians varying key parameters, which informed a comprehensive estimate of the budget for a stage 1 submission to the National Institute for Health and Care Research Efficacy and Mechanism Evaluation programme. Setting International collaboration. Participants Clinicians, researchers, patient and public involvement groups, cerebral cavernous malformations research networks, and commercial partners. Results There was one face-to-face meeting, nine virtual meetings of the co-applicants, and five meetings of the patient and public involvement advisory group. We identified 14 countries with clinical leadership, a cerebral cavernous malformation research network, and a funding agency that could support an international trial. We contacted three potential commercial partners and obtained one letter of collaboration. We sent monthly newsletters to collaborators. Our meetings and simulations concluded that a three-arm, two-stage multiarm multistage adaptive treatment selection randomised trial design was suitable for evaluating aspirin and propranolol as the first two interventions compared with standard care in a platform trial. We submitted a stage 1 proposal for this Cavernous malformations A Randomised Efficacy MAster Protocol study to the National Institute for Health and Care Research Efficacy and Mechanism Evaluation call 23/15 in May 2023, and a resubmission was encouraged. Limitations The National Institute for Health and Care Research Efficacy and Mechanism Evaluation funding committee would have required further justification for the choice of the intermediate phenotype used for treatment selection, biomarker validation work, and details about the pipeline of interventions. Future work We have addressed these limitations and re-applied to the National Institute for Health and Care Research Efficacy and Mechanism Evaluation programme. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme as award number NIHR153811.
Nepal Mediciti Medical Journal · 2023 · 0 citations · open access
Surgical Treatment of Cerebral cavernous Malformations: Report of 6 Cases and pertinent Literature review
AbstractCerebral cavernous Malformation (CCM) is a rare neurovascular malformation accounting 0.5% to 4% of all intracranial vascular malformations. People harboring CCM may be symptomatic or may present with seizure, hemorrhage or progressive neurological deficit. Asymptomatic CCM needs no treatment. The symptomatic CCM may or may not require intervention. The best treatment for symptomatic CCM is microsurgical excision. Over a period of five years we have been managing I2 patients with CCM, and out of them 6 patients who were symptomatic required microsurgical excision. Here, we discuss these 6 surgically managed patients and appropriate literature related to CCMs would be reviewed.
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.
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