DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Marfan syndrome — screening already-approved drugs against its 24-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMarfan syndrome maps to a 24-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 marfan 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
transforming growth factor beta receptor 2 (TGFBR2) — TGFBR2 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 6-methoxypyridin-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5QIN · 1.57 Å · ligand N-{4-[3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide (J2V). Experimental structure, not a prediction.
What the evidence adds up to
One open-label randomised trial of 70 people with Marfan syndrome compared propranolol to no treatment over an average of 9.3 to 10.7 years. Beta-blocker therapy did not reduce all-cause mortality (relative risk 0.24, 95% CI 0.01 to 4.75, low-quality evidence). There was no difference between groups in a composite of aortic dissection, aortic regurgitation, cardiovascular surgery or congestive heart failure (relative risk 0.79, 95% CI 0.37 to 1.69, low-quality evidence). For aortic dissection alone the relative risk was 0.59 (95% CI 0.12 to 3.03). The trial was judged at high risk of selection, performance, detection, attrition and reporting bias.
The same study reported a reduced rate of aortic dilatation measured by M-mode echocardiography in the treatment group (aortic ratio mean slope 0.084 in controls versus 0.023 in the treatment group, P < 0.001). The authors note that it is not known whether this statistically significant difference in a surrogate endpoint translates into clinical benefit in terms of aortic dissection or mortality. No data were reported on change in blood pressure, total adverse events or withdrawals due to adverse events at study end point.
A 2017 Cochrane review concluded that no definitive conclusions for clinical practice could be drawn from this single low-quality trial. The review called for high-quality randomised trials that report all clinically relevant end points and adverse events. A 2010 review described the discovery that the genetic lesion in Marfan syndrome impairs transforming growth factor-beta regulation, and noted that this had led to the first pharmacological intervention in a connective-tissue disorder otherwise incurable by gene-based or stem cell-based strategies, but did not report trial data.
What is still missing are adequately powered, blinded randomised trials that measure aortic dissection and mortality as primary outcomes, that report adverse events systematically, and that test beta-blockers against placebo or against other drug classes such as angiotensin receptor blockers. The single existing trial is too small and too biased to guide treatment decisions.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cochrane Database of Systematic Reviews · 2017 · 47 citations · open access
Beta-blockers for preventing aortic dissection in Marfan syndrome
AbstractBACKGROUND: Marfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural and pulmonary systems. Aortic root dilatation is the most frequent cardiovascular manifestation and its complications, including aortic regurgitation, dissection and rupture are the main cause of morbidity and mortality. OBJECTIVES: To assess the long-term efficacy and safety of beta-blocker therapy as compared to placebo, no treatment or surveillance only in people with Marfan syndrome. SEARCH METHODS: We searched the following databases on 28 June 2017; CENTRAL, MEDLINE, Embase, Science Citation Index Expanded and the Conference Proceeding Citation Index - Science in the Web of Science Core Collection. We also searched the Online Metabolic and Molecular Bases of Inherited Disease (OMMBID), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 June 2017. We did not impose any restriction on language of publication. SELECTION CRITERIA: All randomised controlled trials (RCTs) of at least one year in duration assessing the effects of beta-blocker monotherapy compared with placebo, no treatment or surveillance only, in people of all ages with a confirmed diagnosis of Marfan syndrome were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for inclusion, extracted data and assessed trial quality. Trial authors were contacted to obtain missing data. Dichotomous outcomes will be reported as relative risk and continuous outcomes as mean differences with 95% confidence intervals. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: One open-label, randomised, single-centre trial including 70 participants with Marfan syndrome (aged 12 to 50 years old) met the inclusion criteria. Participants were randomly assigned to propranolol (N = 32) or no treatment (N = 38) for an average duration of 9.3 years in the control group and 10.7 years in the treatment group. The initial dose of propranolol was 10 mg four times daily and the optimal dose was reached when the heart rate remained below 100 beats per minute during exercise or the systolic time interval increased by 30%. The mean (± standard error (SE)) optimal dose of propranolol was 212 ± 68 mg given in four divided doses daily.Beta-blocker therapy did not reduce the incidence of all-cause mortality (RR 0.24, 95% CI 0.01 to 4.75; participants = 70; low-quality evidence). Mortality attributed to Marfan syndrome was not reported. Non-fatal serious adverse events were also not reported. However, study authors report on pre-defined, non-fatal clinical endpoints, which include aortic dissection, aortic regurgitation, cardiovascular surgery and congestive heart failure. Their analysis showed no difference between the treatment and control groups in these outcomes (RR 0.79, 95% CI 0.37 to 1.69; participants = 70; low-quality evidence).Beta-blocker therapy did not reduce the incidence of aortic dissection (RR 0.59, 95% CI 0.12 to 3.03), aortic regurgitation (RR 1.19, 95% CI 0.18 to 7.96), congestive heart failure (RR 1.19, 95% CI 0.18 to 7.96) or cardiovascular surgery, (RR 0.59, 95% CI 0.12 to 3.03); participants = 70; low-quality evidence.The study reports a reduced rate of aortic dilatation measured by M-mode echocardiography in the treatment group (aortic ratio mean slope: 0.084 (control) vs 0.023 (treatment), P < 0.001). The change in systolic and diastolic blood pressure, total adverse events and withdrawal due to adverse events were not reported in the treatment or control group at study end point.We judged this study to be at high risk of selection (allocation concealment) bias, performance bias, detection bias, attrition bias and selective reporting bias. The overall quality of evidence was low. We do not know whether a statistically significant reduced rate of aortic dilatation translates into clinical benefit in terms of aortic dissection or mortality. AUTHORS' CONCLUSIONS: Based on only one, low-quality RCT comparing long-term propranolol to no treatment in people with Marfan syndrome, we could draw no definitive conclusions for clinical practice. High-quality, randomised trials are needed to evaluate the long-term efficacy of beta-blocker treatment in people with Marfan syndrome. Future trials should report on all clinically relevant end points and adverse events to evaluate benefit versus harm of therapy.
Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine · 2010 · 17 citations
Drug‐Based Therapies for Vascular Disease in Marfan Syndrome: From Mouse Models to Human Patients
AbstractMarfan syndrome is a congenital disorder of the connective tissue with a long history of clinical and basic science breakthroughs that have forged our understanding of vascular-disease pathogenesis. The biomedical importance of Marfan syndrome was recently underscored by the discovery that the underlying genetic lesion impairs both tissue integrity and transforming growth factor-beta regulation of cell behavior. This discovery has led to the successful implementation of the first pharmacological intervention in a connective-tissue disorder otherwise incurable by either gene-based or stem cell-based therapeutic strategies. More generally, information gathered from the study of Marfan syndrome pathogenesis has the potential to improve the clinical management of common acquired disorders of connective-tissue degeneration.
Pan African Medical Journal · 2018 · 5 citations · open access
Marfans syndrome: a case report and pictorial essay
AbstractWe report a case of Marfan syndrome (MFS) in a South African patient, which is extraordinary because of the large constellation of clinical, radiological and vascular anomalies in a single patient. A literature search from 1950 to date did not show a similar report of such extensive clinical characteristics of MFS.
Kazan medical journal · 1983 · 0 citations · open access
An atypical case of Marfan syndrome
AbstractMarfan syndrome is a relatively rare disease characterized by a primary congenital defect of connective tissue, which is based on dystrophic changes in fibrous structures caused by impaired metabolism of chondroitinseric and glucuronic acid. The classic signs of this syndrome are lesions of the musculoskeletal system, eyes, heart and large vessels.
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.
