DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cerebral cavernous malformation 1 — screening already-approved drugs against its 2-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 1 maps to a 2-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 cerebral cavernous malformation 1 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 malformation is a rare neurovascular malformation accounting for 0.5% to 4% of all intracranial vascular malformations. Asymptomatic CCM requires no treatment. For symptomatic CCM, the best treatment reported is microsurgical excision. In one series of 12 patients managed over five years, 6 symptomatic patients underwent microsurgical excision. In a separate retrospective study of 12 patients with supratentorial cavernous malformations operated on between June 2014 and December 2016, total resection was achieved in 11 patients (91.7%), and total resection of the surrounding hemosiderin-stained brain was achieved in 9 patients (75%). Improvement of pre-operative symptoms was achieved in 11 patients (91.7%), while post-operative complications occurred in 2 patients (16.6%). The authors concluded that surgical excision of symptomatic supratentorial cavernous malformations provides good control of pre-operative symptoms with low morbidity and mortality.
The familial form of CCM is due to autosomal dominant mutations in the genes KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3. Patients with PDCD10 mutations usually have symptom onset at an early age and a more aggressive phenotype. In a 2022 study, two patients with CCM3 mutations were compared with five patients with familial CCM from CCM1 or CCM2 mutations and six patients with sporadic CCM. The two CCM3 patients had early symptom onset and a high lesion burden. Sequencing showed one patient had a frameshift mutation (c.222delT;p.Asn75ThrfsTer14) and the other a variant in the splicing region c.475-2A>G (p.A119Gfs*42). mRNA expression was 4-fold lower in both CCM3 patients. In silico analysis predicted that the frameshift mutation transcript lacks the C-terminal FAT-homology domain but preserves the N-terminal dimerization domain. The study also suggested a possible link between low-grade astrocytomas and PDCD10 CCM as a manifestation of syndromic disease.
The surgical series are small, with 6 and 12 patients respectively, and the genetic study includes only two CCM3 patients. No controlled trials comparing surgery to observation or to any drug therapy are reported. What is still missing is prospective, multi-centre data with standardised outcome measures, and any evidence for a drug that could alter the natural history of the disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurosurgery · 2017 · 491 citations · open access
Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations Based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel
AbstractBACKGROUND: Despite many publications about cerebral cavernous malformations (CCMs), controversy remains regarding diagnostic and management strategies. OBJECTIVE: To develop guidelines for CCM management. METHODS: The Angioma Alliance ( www.angioma.org ), the patient support group in the United States advocating on behalf of patients and research in CCM, convened a multidisciplinary writing group comprising expert CCM clinicians to help summarize the existing literature related to the clinical care of CCM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and radiology standards, (4) neurosurgical considerations, and (5) neurological considerations. The group reviewed literature, rated evidence, developed recommendations, and established consensus, controversies, and knowledge gaps according to a prespecified protocol. RESULTS: Of 1270 publications published between January 1, 1983 and September 31, 2014, we selected 98 based on methodological criteria, and identified 38 additional recent or relevant publications. Topic authors used these publications to summarize current knowledge and arrive at 23 consensus management recommendations, which we rated by class (size of effect) and level (estimate of certainty) according to the American Heart Association/American Stroke Association criteria. No recommendation was level A (because of the absence of randomized controlled trials), 11 (48%) were level B, and 12 (52%) were level C. Recommendations were class I in 8 (35%), class II in 10 (43%), and class III in 5 (22%). CONCLUSION: Current evidence supports recommendations for the management of CCM, but their generally low levels and classes mandate further research to better inform clinical practice and update these recommendations. The complete recommendations document, including the criteria for selecting reference citations, a more detailed justification of the respective recommendations, and a summary of controversies and knowledge gaps, was similarly peer reviewed and is available on line www.angioma.org/CCMGuidelines .
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.
The Medical Journal of Cairo University/The Medical Journal of Cairo University · 2020 · 0 citations · open access
Supratentorial Cavernous Malformations: Surgical Management and Outcome
AbstractBackground: Cavernous malformations are common vas-cular malformations composed of thin-walled sinusoids with no intervening brain parenchyma. Aim of Study: To evaluate the outcome of surgical resection of supratentorial cavernous malformations. Patients and Methods: 12 patients with supratentorial cavernous malformations operated upon in the period from June 2014 to December 2016 in Cairo University Hospitals were retrospectively studied for surgical outcomes including extent of excision, improvement of symptoms and development of complications. Pre-operative CT and MRI were performed in all patients in addition to angiography when the diagnosis was doubtful. Patients were followed-up clinically and radi-ologically for 1 year after surgery. Results: The study included 6 males and 6 females with an average age of 34.6 years. The lesion was frontal in 4, temporal in 4, parietal in 3 and occipital in 1 patient. Epilepsy was the most common presenting symptom occurring in 6 patients. Total resection was achieved in 11 (91.7%) patients. Total resection of the surrounding hemosiderin-stained brain was achieved in 9 (75%) patients. Improvement of pre-operative symptoms was achieved in 11 (91.7%) patients. Post-operative complications occurred in 2 (16.6%) patients. Conclusions: Surgical excision of symptomatic supraten-torial cavernous malformations provides good control of pre-operative symptoms and has a low rate of morbidity and mortality. The aim of surgery should always be total excision of the malformation.
Research Square · 2022 · 0 citations · open access
Comprehensive CCM3 Mutational Analysis in Patients with Syndromic Cerebral Cavernous Malformation
AbstractAbstract Cerebral Cavernous Malformation (CCM) is a vascular disease that affects the central nervous system, which familial form is due to autosomal dominant mutations in the genes KRIT1/CCM1 , MGC4607/CCM2 and PDCD10/CCM3 . Patients affected by the PDCD10 mutations usually have the onset of symptoms at an early age and a more aggressive phenotype. To contribute to knowledge about the disease, we performed clinical, functional, and neuroradiological analyses of the mutations in PDCD10/CCM3 in two patients comparing the findings with five patients with familial form from CCM1/KRIT1 or CCM2/MGC4607 mutations and six patients with sporadic form. In addition, we have evaluated the PDCD10/CCM3 gene expression by qPCR and developed a bioinformatic pipeline to assist in the possible clinical. The two CCM3 patients had an early onset of symptoms and a high lesion burden. Furthermore, the sequencing showed that P1 had a frameshift mutation (c.222delT;p.Asn75ThrfsTer14) and P2 a variant on the splicing region c.475-2A > G (p.A119Gfs*42). The mRNA expression was 4-fold lower in both patients with PDCD10/CCM3 mutation. In silico analysis, the prediction reveals that the frameshift mutation transcript lacks the C-terminal FAT-homology domain compared to the 212 aa-length wild-type PDCD10/CCM3 and preserves the N-terminal dimerization domain. We also demonstrated a related pathway that might explain the interplay between low-grade astrocytomas and PDCD10 CCM, a possible manifestation of the syndromic disease. The two mutations support the understanding of the protein-protein interaction between PDCD10 and several essential cellular proteins that might contribute to the mechanistic understanding of why some individuals with CCM3 have a syndromic phenotype.
Digital Diagnostics · 2021 · 0 citations · open access
Cavernous malformations of the brain and modern views on their treatment
AbstractCavernous malformations of the brain have become an increasingly common pathology in recent years, thanks to the advancement of modern methods of neuroimaging. Despite the benign nature of the course in most cases, these formations can cause convulsions and serious neurological disorders. Typically, clinical manifestations are caused by hemorrhages in the structure of the cavernous and surrounding parenchyma of the brain. The management strategy chosen for patients with cerebral cavernous malformations is determined by the type of malformation, its size, localization, the presence of repeated hemorrhages, and the clinical picture. This literature review focuses on modern methods of treating cerebral cavernous malformations. The main methods of treatment for cavernous malformations of the brain, particularly surgical treatment, have been analyzed. If surgical intervention is not possible, alternative methods of treatment include radiation therapy, such as stereotaxic radiosurgery, and proton therapy, in cases of deep location of foci in functionally significant areas of the brain, which are characterized by the highest risk of complications. Thе possibilities, efficacy, and safety of stereotactic radiosurgical treatment are discussed, as well as the use of proton therapy in the treatment of cavernous malformations. Furthermore, radiation therapy has been shown to be beneficial for cavernous malformations.
Public health of the Far East Peer-reviewed scientific and practical journal · 2025 · 0 citations
A Case of Successful Surgical Treatment of a Patient with a Brainstem Cavernoma
AbstractThis article presents a clinical case of successful surgical treatment of a patient with a rare vascular pathology of the central nervous system – a cavernous malformation of the brainstem. The relevance of this problem is due to the complexity of surgical treatment of cavernomas, their poor anatomical accessibility, the need for modern neuroimaging methods, and the high risk of hemorrhage and adverse clinical outcome.
Supplementary Material for: Cavernous Malformation Hemorrhagic Presentation at Diagnosis Associated with Low 25-Hydroxy-Vitamin D Level
Abstract<b><i>Background:</i></b> Cavernous malformations (CM) are angiographically occult vascular malformations that may be incidental or present with intracerebral or spinal hemorrhage, seizures, or nonhemorrhagic focal neurologic deficit (FND). Recently in vitro data have suggested vitamin D may play a role in stabilizing CCM2 endothelial cells. Little is known about the effect of vitamin D in human CM disease. <b><i>Methods:</i></b> Beginning in 2015, consecutive patients at our institution with radiologically confirmed CM were recruited to participate in a prospective clinical registry as well as 25-hydroxy-vitamin D study. A structured interview, survey, and examination were performed at baseline. Medical records and magnetic resonance imaging studies were reviewed and data collected included comorbid conditions, medication use, and location of CM. Standard definition of clinical hemorrhage, FND, and seizures was used. Univariate and multivariate logistic regression models were used, and OR, 95% CIs, and likelihood-ratio <i>p</i> values were calculated to determine the influence of the 25-hydroxy-vitamin D level on clinical presentation with hemorrhage. <b><i>Results:</i></b> Of 213 patients enrolled in the clinical registry between January 2015 and October 2018, 70 participated in the vitamin D study (median age: 38.3 years; 51.4% female). Of the 70 participants, 30 (42.9%) presented with hemorrhage. 25-Hydroxy-vitamin D levels were performed within 1 year of symptoms in 64.1% of patients. Patients presenting with hemorrhage had a lower 25-hydroxy-vitamin D level compared to those presenting with seizure without hemorrhage, FND, or as an incidental finding (median 25.5 ng/mL; range 11–59 hemorrhage vs. median 31.0; range 14–60, no hemorrhage; <i>p</i> = 0.04). After adjusting for age, month of blood draw, and body mass index, 25-hydroxy-vitamin D remained a significant predictor of hemorrhagic presentation. Brainstem location also predicted hemorrhage at presentation. <b><i>Conclusion:</i></b> Low 25-hydroxy-vitamin D level was more common in patients with CM presenting with hemorrhage. This study supports the potential role of modifiable factor in the initial clinical presentation of CM. Further study is needed to determine the role of vitamin D on prospective hemorrhage risk and whether supplementation may be beneficial.
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.
