DeCure for Idiopathic pulmonary arterial hypertension
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for idiopathic pulmonary arterial hypertension — screening already-approved drugs against its 9-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIdiopathic pulmonary arterial hypertension maps to a 9-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 idiopathic pulmonary arterial hypertension 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
bone morphogenetic protein receptor type 2 (BMPR2) — BMPR2 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6UNP · 2.3 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
In a Norwegian cohort of 32 newly diagnosed patients with idiopathic pulmonary arterial hypertension, updated treatment (including drugs repurposed from other indications) produced significant improvements in haemodynamics and physical capacity that persisted over follow-up. The patients were 78% women, mean age 42 years, in NYHA class 2.9, with maximal oxygen uptake 12.0 ml/kg/min (37% of expected). During a mean follow-up of 43 months, seven patients died and two underwent bilateral lung transplantation. Observed transplantation-free survival was 81% at one, two and three years, compared with an estimated transplantation-free survival of 70%, 58% and 49% from the era when only conventional treatment was available. The authors state that mortality remains high but is probably lower than before.
Drug repurposing has been a notable success in pulmonary arterial hypertension, with positive large phase 3 trials for epoprostenol, bosentan, iloprost, and sildenafil. Despite these multiple available therapies, mortality rates have changed only modestly, and patients remain highly symptomatic, frequently ending up on parenteral therapy and lung transplant waiting lists. The Pulmonary Vascular Research Institute's Innovative Drug Development Initiative has identified an unmet need for new treatments and considers drug repurposing an important avenue to address this problem.
The pathogenesis of pulmonary arterial hypertension involves endothelial dysfunction as a central mechanism, with both genetic predispositions and environmental factors contributing to onset. A comprehensive review of endothelial function in the disease has been published to support development of future therapies. Current treatment algorithms are based on evidence from randomised clinical trials showing useful effects of various drugs, but treatment is still described as frequently deficient and empirical.
What remains missing is a trial design that can reliably identify which repurposed candidates will meaningfully alter the high residual mortality, and the funding to test them in adequately powered studies. Patient stratification by endothelial dysfunction phenotype or genetic background has not been incorporated into repurposing trials, and no single agent has yet been shown to eliminate the need for transplantation or parenteral therapy in the majority of patients.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Medicine · 2024 · 19 citations · open access
Endothelial Function in Pulmonary Arterial Hypertension: From Bench to Bedside
AbstractPulmonary arterial hypertension is a complex pathology whose etiology is still not completely well clarified. The pathogenesis of pulmonary arterial hypertension involves different molecular mechanisms, with endothelial dysfunction playing a central role in disease progression. Both individual genetic predispositions and environmental factors seem to contribute to its onset. To further understand the complex relationship between endothelial and pulmonary hypertension and try to contribute to the development of future therapies, we report a comprehensive and updated review on endothelial function in pulmonary arterial hypertension.
Pulmonary Circulation · 2020 · 13 citations · open access
Repurposing of medications for pulmonary arterial hypertension
AbstractThis manuscript on drug repurposing incorporates the broad experience of members of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative as an open debate platform for academia, the pharmaceutical industry and regulatory experts surrounding the future design of clinical trials in pulmonary hypertension. Drug repurposing, use of a drug in a disease for which it was not originally developed, in pulmonary arterial hypertension has been a remarkable success story, as highlighted by positive large phase 3 clinical trials using epoprostenol, bosentan, iloprost, and sildenafil. Despite the availability of multiple therapies for pulmonary arterial hypertension, mortality rates have modestly changed. Moreover, pulmonary arterial hypertension patients are highly symptomatic and frequently end up on parental therapy and lung transplant waiting lists. Therefore, an unmet need for new treatments exists and drug repurposing may be an important avenue to address this problem.
Tidsskrift for Den norske legeforening · 2011 · 1 citations · open access
Behandling av idiopatisk pulmonal arteriell hypertensjon
AbstractBACKGROUND: In the past 5-10 years, drug treatment of idiopathic pulmonary arterial hypertension has evolved considerably. Experience and results from use of such updated treatment in Norway has not been reported. MATERIAL AND METHOD: 32 patients newly diagnosed with idiopathic pulmonary arterial hypertension, were consecutively assessed with respect to hemodynamics and physical capacity. The results after three months were compared with those after 12 months. Observed survival was compared with estimated survival from the time when only conventional treatment was available. RESULTS: The patients (78% women) were 42 ± 14 years, had dyspnea in NYHA class 2.9 ± 0.4 and a maximal oxygen uptake of 12.0 ± 3.9 ml/kg/min (37 ± 13% of the expected). Updated treatment led to significantly improved hemodynamics and physical capacity, which persisted during follow-up. During 43 ± 31 months follow-up, seven patients died while two underwent bilateral lung transplantation. Observed transplantation-free survival was 81% after one, two and three years, while that for estimated transplantation-free survival was 70%, 58% and 49% respectively. INTERPRETATION: Treatment of idiopathic pulmonary arterial hypertension with updated treatment improves hemodynamics and thereby symptoms. Mortality remains high, but is probably lower than it was when only conventional treatment was available.
sj-pdf-1-pul-10.1177_2045894021995055 - Supplemental material for A minimal clinically important difference measured by the Cambridge Pulmonary Hypertension Outcome Review for patients with idiopathic pulmonary arterial hypertension
AbstractSupplemental material, sj-pdf-1-pul-10.1177_2045894021995055 for A minimal clinically important difference measured by the Cambridge Pulmonary Hypertension Outcome Review for patients with idiopathic pulmonary arterial hypertension by Katherine Bunclark, Natalie Doughty, Alice Michael, Nisha Abraham, Samantha Ali, John E Cannon, Karen Sheares, Nicola Speed, Dolores Taboada, Mark Toshner and Joanna Pepke-Zaba in Pulmonary Circulation
Current Respiratory Medicine Reviews · 2007 · 0 citations
Current Treatment of the Pulmonary Arterial Hypertension
AbstractPulmonary arterial hypertension is a feature of a spectrum of diseases that includes elevated pulmonary vascular resistance, induces right ventricular insufficiency and heart failure, and threatens the life. The aetiology and pathogenesis is diverse and associated with elevated morbidity and mortality. Treatment is frequently deficient and empirical. Fortunately, in recent years, randomized clinical trials have shown useful effects of various drugs on pulmonary arterial hypertension. This article reviews the pharmacological and not pharmacological therapeutic options to treat pulmonary arterial hypertension and attempts to provide a proposal of algorithm for its management based upon the evidence and available guidelines for clinical management. Keywords: Pulmonary arterial hypertension, treatment
Current and Emerging Therapies for Pulmonary Arterial Hypertension
AbstractPulmonary arterial hypertension (PAH) is a complex and progressive disease of the pulmonary vasculature that requires targeted medical management for symptom control and improved survival. Use of targeted treatments requires specialized training. In less than 2 decades, multiple targeted treatment options, including oral, inhaled, and infused therapies, have been introduced and many more therapeutic developments are in the pipeline. Agents under investigation include new medications that target established pathways as well as those that target recently identified underlying mechanisms of PAH. In the next few years, multiple agents are anticipated to receive approval and will further shape the evolving treatment domain of PAH.
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.
