DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for familial bicuspid aortic valve — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial bicuspid aortic valve maps to a 4-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 familial bicuspid aortic valve 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
NK2 homeobox 5 (NKX2-5) — NKX2-5 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6WC2 · 2.1 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1997 retrospective study of 54 children and adolescents who received mechanical aortic valve replacement reported early mortality of 13% overall, falling to 6% in the 32 patients operated on after 1984. Over a total follow-up of 261 patient-years, there were six late deaths, two of which were valve-related (one gastrointestinal bleed, one massive thromboembolism). Linearised rates of valve thrombosis and anticoagulant-related haemorrhage were both 0.3% per patient-year. Actuarial survival was 84.5% at five years and 70.2% at ten years. The authors concluded the long-term outcome was satisfactory and comparable to biological substitutes, with warfarin tolerated in this age group.
A 2005 study of the Ross procedure in 27 infants under 18 months (median age 5.7 months) with congenital aortic stenosis reported three early deaths and no late deaths over a median follow-up of 6.1 years. Freedom from homograft reintervention was 87% at eight years; freedom from autograft reintervention was 100%. Among 17 patients with follow-up echocardiograms, one had an estimated peak autograft gradient of 55 mm Hg; 16 had gradients below 10 mm Hg. Mild autograft insufficiency was seen in four patients; 13 had none. Autograft diameter z scores increased significantly from the postoperative period to one year at both the annulus and sinus, then stabilised. The authors noted dilatation of the autograft occurred during the first year after surgery and did not progress thereafter.
A 2023 report from Toronto General Hospital described 404 patients who underwent reimplantation of a tricuspid aortic valve, with a median follow-up of 11.7 years. Cumulative mortality at 20 years was 26.7%, the cumulative incidence of reoperation on the aortic valve was 7.0%, and development of moderate or severe aortic insufficiency was 11.8%. No variables were identified that predicted reoperation or aortic insufficiency. New distal aortic dissections were common in patients with associated genetic syndromes such as Marfan or Loeys-Dietz. The authors concluded that reimplantation provides excellent aortic valve function during the first two decades but noted distal aortic dissections in syndromic patients.
A 2023 review of paediatric bicuspid aortic valve and its associated aortopathy stated that progressive aortic dilation is common in children with bicuspid aortic valve and is linked to increased risk of aneurysm, dissection, and surgery in adulthood. The review highlighted high familial incidence, the safety of recreational physical activity for most affected children, the potential for medical management to slow aortic growth, and the feasibility of paediatric registries for longitudinal evaluation. A 2008 Canadian retrospective cohort of 642 ambulatory adults with bicuspid aortic valve was mentioned but no numerical outcomes were provided in the abstract. A 2018 review noted that bicuspid aortic valve affects 1–2% of births and is frequently associated with thoracic aortic aneurysm, but the risk of aortic dissection is low; aortic surgery is recommended when the maximum aortic diameter exceeds 55 mm, or at an earlier stage with risk factors such as family history of dissection or rapid progression.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Cardio-Thoracic Surgery · 1997 · 43 citations · open access
Mechanical valve in aortic position is a valid option in children and adolescents1
AbstractOBJECTIVE: The choice of a valve substitute remains a challenge in young patients, with numerous reports of early degeneration and calcification of biological valves in this age group. Therefore an assessment of the long-term results after mechanical aortic valve replacement in children was initiated. METHODS: A retrospective study was conducted in 54 consecutive patients aged 1.1 to 17 years (mean 12.8 +/- 4 years) operated on between 1975 and 1993. Aetiology was congenital in 34 patients, rheumatic in 13, infectious in 5, and dystrophic in 2. Concomitant surgery included mitral valve replacement (10), aortic annulus enlargement (9), correction of truncus arteriosus (7), Bentall operation (2), coarctation repair (2), tricuspid valvuloplasty (2), correction of double outlet right ventricle (1), and replacement of a right ventricle to pulmonary artery conduit (1). A Bjork-Shiley valve was implanted in 14 patients, and a St Jude Medical valve in 40. All patients were given Warfarin with a monthly INR control. Follow-up was completed through questionnaires mailed to referring physicians and direct clinical examination. RESULTS: Overall early mortality was 13% (7 cases), and 6% (2 cases) in the 32 patients operated on after 1984. Follow-up was complete in 45 survivors (2 lost to follow-up), with a total follow-up of 261 patient-years. There were 6 late deaths, 4 being cardiac and due to persistent LV dysfunction, and 2 valve-related, due respectively to major gastro-intestinal bleeding and massive thromboembolism. Linearized rates of valve thrombosis and anticoagulant-related hemorrhage were both 0.3% per patient-year. Actuarial survival rate was respectively 84.5% at 5 years and 70.2% at 10 years. Reoperation was necessary in 3 patients for recurrent LV outflow tract obstruction. One patient with severe LV dysfunction is awaiting a heart transplant. CONCLUSION: We conclude that the longterm outcome after mechanical aortic valve replacement in children and adolescents is satisfactory and comparable to currently available reports on biological substitutes. The mandatory anticoagulant therapy is well tolerated in this age group.
Ross Procedure in Infants and Toddlers Followed Into Childhood
AbstractBACKGROUND: The Ross procedure is commonly used to treat aortic valve disease in pediatric and adult patients. For infants, data are limited regarding survival, reintervention, autograft growth, and function. METHODS AND RESULTS: The Ross procedure was performed in 27 infants <18 months of age (median age 5.7 months). All patients had congenital aortic stenosis (AS); associated lesions included subAS (n=9), supravalvular AS (n=2), coarctation (n=5), and interrupted aortic arch (n=2). Median follow-up was 6.1 years (range 0.2 to 12.9). There were 3 early deaths and no late deaths. Freedom from reintervention for homograft dysfunction was 87% at 8 years; freedom from autograft reintervention was 100%. Follow-up echocardiograms were available in 17 patients. Estimated peak autograft gradient was 55 mm Hg in one patient and <10 mm Hg in 16. Mild autograft insufficiency was seen in 4 patients; 13 had none. Autograft diameter was measured early postoperatively and at latest follow-up. The mean z score increased from 0.63 to 3.2 (P<0.01) at the annulus and from 0.26 to 2.2 (P<0.01) at the sinus. In a subgroup, the mean autograft z score increased significantly from the postoperative period to 1 year for both the annulus (0.72 to 3.2, P<0.01) and the sinus (0.26 to 2.2, P<0.01), but remained unchanged thereafter. CONCLUSIONS: The Ross procedure effectively relieves AS in infants. Homograft reintervention occurred in 13% within 8 years. No patient developed significant autograft insufficiency or required autograft reintervention during the follow-up period. Dilatation of the autograft occurred during the first year after surgery and stabilized thereafter.
Annals of Cardiothoracic Surgery · 2023 · 19 citations · open access
Reimplantation of the aortic valve in patients with tricuspid aortic valve: the Toronto General Hospital experience
AbstractBackground: Aortic valve sparing operations were introduced three decades ago but controversy remains regarding its appropriateness, reproducibility and durability. This article describes the long-term outcomes of patients who had reimplantation of the aortic valve. Methods: All patients who had reimplantation of a tricuspid aortic valve at Toronto General Hospital from 1989 through 2019 were selected for this study. Patients were followed prospectively with periodical clinical assessments and imaging of the heart and aorta. Results: Four hundred and four patients were identified. The median age was 48.0 [interquartile range (IQR), 35.0-59.0] years and 310 (76.7%) were men. There were 150 patients with Marfan syndrome, 20 with Loeys-Dietz syndrome and 33 with acute or chronic aortic dissections. The median follow-up was 11.7 (IQR, 6.8-17.1) years. There were 55 patients alive and without reoperation at 20 years. The cumulative mortality at 20 years was 26.7% [95% confidence interval (CI): 20.6-34.2%], the cumulative incidence of reoperation on the aortic valve was 7.0% (95% CI: 4.0-12.2%) and the development of moderate or severe aortic insufficiency was 11.8% (95% CI: 8.5-16.5%). We could not identify variables associated with reoperation on the aortic valve or with the development of aortic insufficiency. New distal aortic dissections were common in patients with associated genetic syndromes. Conclusions: Reimplantation of the aortic valve in patients with tricuspid aortic valve provides excellent aortic valve function during the first two decades of follow-up. Distal aortic dissections are relatively common in patients with associated genetic syndromes.
The congenital bicuspid aortic valve with post-inflammatory disease—a neglected pathological diagnosis of clinical relevance
AbstractIt is unusual to find surgically excised congenital bicuspid aortic valves with post-inflammatory disease. We have analysed retrospectively all surgically excised aortic valves over a 6-year period for this particular diseased state in relation to relevant clinical data. There were 181 congenital bicuspid aortic valves, and the characteristic gross pathology of the tricuspid aortic valve with post-inflammatory disease served as reference. Twelve of the 181 congenital bicuspid aortic valves were identified as post-inflammatory (6.6%); one with clinically established rheumatic disease. The mean age at operation of these 12 patients was significantly lower compared to 'other' aortic valves. The study indicates that post-inflammatory involvement of a congenital bicuspid aortic valve can be identified, which is of clinical relevance since these patients have a significantly younger age at operation.
Current Opinion in Pediatrics · 2023 · 2 citations
Bicuspid aortic valve and its ascending aortopathy
AbstractPURPOSE OF REVIEW: To synthesize and critically assess recent clinical and research advancements in pediatric bicuspid aortic valve (BAV) and its associated aortopathy. RECENT FINDINGS: In pediatric patients with BAV, progressive aortic dilation (i.e. bicuspid aortopathy) is commonly present and associated with increased risk for aortic aneurysm, dissection, and surgery in adulthood. Ongoing research explores the cause, incidence, and progression of bicuspid aortopathy to promote earlier diagnosis and improve preventive management. Recent findings include: high familial incidence and need for improved familial screening; safety of recreational physical activity in most affected children; potential for medical management to slow aortic growth; feasibility of pediatric registries to evaluate longitudinal outcomes; and potential genetic and hemodynamic biomarkers for disease risk stratification. SUMMARY: Pediatric bicuspid aortopathy is an important area for investigation and preventive management to improve long-term cardiovascular outcomes. Recent literature promotes familial screening, recreational exercise, medical prophylaxis, registry-based longitudinal evaluation, and continued scientific inquiry.
Good Prognosis for Adults with Bicuspid Aortic Valves
AbstractBicuspid aortic valve is the most common congenital cardiac abnormality in adults, yet few contemporary data are available on outcomes in this patient population. Now, investigators in Canada have retrospectively assessed a cohort of 642 ambulatory patients with bicuspid aortic valves who were treated at a congenital cardiac disorders center from 1994 through 2001 and were followed for …
Oxford University Press eBooks · 2018 · 0 citations
Genetic diseases of the aorta: aortic diseases related to Marfan syndrome and other genetic abnormalities
AbstractBicuspid aortic valve affects 1–2% of babies at birth and is frequently associated with thoracic aortic aneurysm but the risk of aortic dissection is low. Indications for aortic surgery are based on studies on natural history. Aortic surgery is recommended when the maximum aortic diameter is greater than 55 mm in patients with a bicuspid aortic valve. Intervention is indicated at an earlier stage when there are associated risk factors, in particular familial history of aortic dissection or rapid progression, or if there is an indication for aortic valve replacement. The choice between partial or total replacement of the aorta should be based on anatomy, but also take into account the patient’s age and operative risk.
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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