DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for severe acute respiratory syndrome — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSevere acute respiratory syndrome maps to a 45-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 severe acute respiratory 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
cathepsin L (CTSL) — CTSL 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 eohdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6JD8 · 1.457 Å · ligand ETHANOL (EOH). Experimental structure, not a prediction.
What the evidence adds up to
Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), were first described in 1967. The syndrome causes severe acute respiratory failure with dynamic impairment in oxygen and carbon dioxide transfer, requiring high levels of supplementary oxygen and high minute ventilation. Mortality from ALI/ARDS decreased during the 1990s but still exceeds 30 percent. Despite intense research efforts since 1967, very few therapies have been shown to be effective other than lung protective mechanical ventilation, a strategy that substantially reduced mortality. One other advance, activated protein C for severe sepsis (the leading cause of ALI/ARDS), was noted in 2003, but the 2012 review states that novel drugs studied as potential ARDS-specific therapies have not been shown to improve clinical outcome and cannot be recommended for routine care. The scarcity of therapeutic choices is related to the intricate pathogenesis of the syndrome and to insensitive and aspecific diagnostic criteria.
The development of ALI/ARDS is associated with direct pulmonary injury from pneumonia and aspiration as well as indirect injury from trauma, sepsis, acute pancreatitis, and drug overdose. Although improvements in prevention and treatment have decreased both incidence and mortality, the condition remains a substantial public health problem in the United States, Canada, and worldwide. The goal of fundamental characterisation of ALI/ARDS in a way that results in highly effective prevention and treatment remains incomplete and elusive. Unacceptable morbidity and mortality persist.
The National Heart, Lung, and Blood Institute convened working groups in 2003 and again in 2020 to develop specific recommendations for future research. These groups recommended improved understanding of disease heterogeneity through evolving biologic, genomic, and genetic approaches, combined with animal and clinical studies. The 2005 review notes that while important discoveries have been made, the fundamental characterisation of the syndrome remains incomplete. The 2015 review summarises advances in new ARDS definitions and provides an overview of new relevant signalling pathways that mediate acute lung injury.
What is still missing is a clear definition of the cellular and molecular events requisite in lung injury and repair that results in highly effective prevention and treatment. The intricate pathogenesis and insensitive diagnostic criteria continue to block progress. No drug has been shown to improve clinical outcome in routine care. The field lacks specific treatments beyond supportive ventilation, and the working group recommendations from 2003 and 2020 both call for more research into disease heterogeneity and better detection methods rather than offering a cure.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Respiratory Cell and Molecular Biology · 2005 · 646 citations · open access
Acute Lung Injury and the Acute Respiratory Distress Syndrome
AbstractIn 2005, the American Thoracic Society marks its 100th year of existence. For over a third of this span, since 1967, clinicians and investigators have struggled with a common, often lethal condition originally termed the adult respiratory distress syndrome (ARDS) (1).* While the syndrome almost certainly occurred in earlier times well before the advent of intensive care units, this date establishes its modern era. Subsequently, ARDS has more correctly come to indicate the acute respiratory distress syndrome because it occurs in children as well as in adults (2). ARDS causes severe acute respiratory failure with dynamic impairment in oxygen and carbon dioxide transfer, with the need for high levels of supplementary oxygen and a high minute ventilation (3, 4). Efforts to understand the pathophysiologic events underlying ARDS, a constellation that is now generally termed acute lung injury (ALI), have been substantial and remain a priority of the National Institutes of Health (5). The expectation has been that basic, translational, and clinical studies will result in new strategies for management of ALI/ARDS based on clear definition of the cellular and molecular events requisite in lung injury and repair. While important discoveries have been made, the goal of fundamental characterization of ALI/ARDS in a way that results in highly effective prevention and treatment remains incomplete and elusive. One major advance in supportive care, a strategy of lung protective mechanical ventilation, has substantially reduced mortality in ALI/ARDS (6, 7). This therapeutic intervention resulted from both experimental and clinical studies that evaluated the effect of different ventilation strategies on the course of ALI, and continues a theme initiated in the original description of ALI/ARDS in which positive end-expiratory pressure was introduced as a management modality (1).
In spite of the advances in supportive care of patients with ALI/ARDS, unacceptable morbidity and mortality persist and formidable challenges remain. Our objective here is to review briefly what we knew in 1967 regarding pathogenesis and what we know in 2005, and to provide a perspective on how insights have evolved over the last four decades.
American Journal of Respiratory and Critical Care Medicine · 2003 · 497 citations
Future Research Directions in Acute Lung Injury: Summary of a National Heart, Lung, and Blood Institute Working Group
AbstractAcute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The development of ALI/ARDS is associated with several clinical disorders including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma, sepsis, and other disorders such as acute pancreatitis and drug overdose. Although mortality from ALI/ARDS has decreased in the last decade, it remains high. Despite two major advances in treatment, low VT ventilation for ALI/ARDS and activated protein C for severe sepsis (the leading cause of ALI/ARDS), additional research is needed to develop specific treatments and improve understanding of the pathogenesis of these syndromes. The NHLBI convened a working group to develop specific recommendations for future ALI/ARDS research. Improved understanding of disease heterogeneity through use of evolving biologic, genomic, and genetic approaches should provide major new insights into pathogenesis of ALI. Cellular and molecular methods combined with animal and clinical studies should lead to further progress in the detection and treatment of this complex disease.
Annals of the American Thoracic Society · 2015 · 160 citations
Mechanisms and Clinical Consequences of Acute Lung Injury
AbstractAcute respiratory distress syndrome (ARDS) was first described in 1967, and since then there have been a large number of studies addressing its pathogenesis and therapies. Despite intense research efforts, very few therapies for ARDS have been shown to be effective other than the use of lung protection strategies. The scarcity of therapeutic choices is related to the intricate pathogenesis of the syndrome and to insensitive and aspecific criteria to diagnose this profound acute respiratory failure. The aim of this paper is to summarize advances of new ARDS definitions and provide an overview of new relevant signaling pathways that mediate acute lung injury.
Future research directions in acute lung injury: Summary of a National Heart, Lung, and Blood Institute Working Group
AbstractAcute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The development of ALI/ARDS is associated with several clinical disorders including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma, sepsis, and other disorders such as acute pancreatitis and drug overdose. Although mortality from ALI/ARDS has decreased in the last decade, it remains high. Despite two major advances in treatment, low VT ventilation for ALI/ARDS and activated protein C for severe sepsis (the leading cause of ALI/ARDS), additional research is needed to develop specific treatments and improve understanding of the pathogenesis of these syndromes. The NHLBI convened a working group to develop specific recommendations for future ALI/ARDS research. Improved understanding of disease heterogeneity through use of evolving biologic, genomic, and genetic approaches should provide major new insights into pathogenesis of ALI. Cellular and molecular methods combined with animal and clinical studies should lead to further progress in the detection and treatment of this complex disease.
Seminars in Respiratory and Critical Care Medicine · 2013 · 11 citations
Acute Lung Injury
AbstractAcute respiratory distress syndrome (ARDS) is a clinical syndrome of acute respiratory failure due to acute lung inflammation and noncardiogenic pulmonary edema that often leads to multiorgan system failure and death. Although improvements in prevention and treatment have decreased both the incidence and the mortality of ARDS, it remains a substantial public health problem in the United States, Canada, and worldwide. In the current issue of Seminars in Respiratory and Critical Care Medicine, 11 articles highlight current clinical management strategies with an emphasis on emerging and future therapies as well as recent topics of major interest in clinical and basic research.
AbstractIn Brief Acute respiratory distress syndrome is a serious complication of critical illness that is associated with high morbidity and mortality. There are no effective treatment options, so prevention, early recognition, and appropriate supportive care are essential to improve outcomes. This article provides an overview of the disorder, including current treatment considerations. Acute respiratory distress syndrome is a serious complication of critical illness that is associated with high morbidity and mortality. Prevention, early recognition, and appropriate supportive care are essential to improve outcomes.
Indian Journal of Critical Care Medicine · 2020 · 2 citations · open access
Indications for Proning in Acute Respiratory Distress Syndrome: Expanding the Horizon!
AbstractBackground: Previously prone positioning (PP) was described in addition to invasive mechanical ventilation and it has been known to reduced mortality and improve oxygenation in patients of ARDS. Recently novel timing of prone positioning was described with the use of high-frequency nasal cannula (HFNC) and noninvasive ventilation (NIV) in patients of acute respiratory distress syndrome (ARDS) to avoid the intubation. Here we would like to share a case of severe ARDS where prone positioning was used in a step further ahead. Case description: A 38-year-old gentleman presented with the complaints of progressive breathlessness, dry cough and fever for 7 days. Patient was diagnosed as a case of H1N1 pneumonia with severe ARDS. Patient was initially managed with invasive mechanical ventilation according to ARDS-Net protocol. Despite persistent hypoxia he was put on prone positioning for consecutive 4 days. Patient was extubated after 10 days of mechanical ventilation and put on HFNC in view of persistent high oxygen requirement. At this point of time, we attempted prone positioning in addition to HFNC. Patient was comfortable on prone position and put himself in the same condition for prolonged periods. His oxygenation showed a remarkable improvement from PaO 2 of 63 (before prone positioning) to 136 mm Hg (after prone positioning). Oxygen supplementation was later tapered off and subsequently, he improved and was shifted to ward. Conclusion: Prone positioning is a harmless and still extremely effective intervention which can and should be utilized at all steps of ARDS-management.
Novel chemotherapies for acute respiratory distress syndrome
AbstractThe fatality rate of acute respiratory distress syndrome (ARDS) has decreased during the 1990s but still exceeds 30％.Management of ARDS is supportive,aimed at improving gas exchange and preventing complications while the underlying disease that precipitated ARDS is treated.Novel drugs which were as potential ARDS specific therapies have been studied.However,they have not been shown to improve clinical outcome and,thus,cannot be recommended for routine care.
Key words:
Acute respiratory distress syndrome; Novel drug
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.
