DeCure for Chronic intestinal vascular insufficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for chronic intestinal vascular insufficiency — screening already-approved drugs against its 23-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChronic intestinal vascular insufficiency maps to a 23-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 chronic intestinal vascular insufficiency 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
prostaglandin I2 synthase (PTGIS) — PTGIS 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 bogdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3B6H · 1.62 Å · ligand octyl beta-D-glucopyranoside (BOG). Experimental structure, not a prediction.
What the evidence adds up to
The 2005 review of inflammatory bowel disease describes diminished mucosal perfusion in chronically inflamed bowel, linked to impaired wound healing and refractory mucosal damage. It questions whether angiogenesis within the gut sustains inflammation or generates shunting of blood away from the mucosal surface, but offers no clinical data on any drug. The 2008 review similarly notes abnormal expression of pro- and anti-angiogenic molecules in IBD and proposes that pathological angiogenesis may maintain inflammation, but again provides no treatment results.
In a 2001 rat model of acute segmental mesenteric vascular occlusion, intra-arterial infusion of papaverine (30 or 40 microg/kg/min) or isoproterenol (0.06 microg/kg/min) for 48 hours failed to improve and actually significantly reduced the length of devascularised bowel maintained viable by collateral blood flow. Norepinephrine (0.1 or 0.2 microg/kg/min) also decreased viable segment length. The authors state that intraarterial vasodilator therapy fails to improve intestinal viability after segmental mesenteric vascular occlusion.
A 2011 German vascular-surgical review notes that chronic progressive occlusive disease of intestinal arteries is most often caused by atherosclerosis, that stenosis >70% produces mesenteric ischaemic pain, and that intestinal infarction carries a mortality of 60–80%. Treatment is indicated for symptomatic disease; endovascular intervention is preferred due to high morbidity in these patients, though the authors note quality improvement is required. Surgical reconstruction of two vessels with antegrade supraceliac revascularisation is recommended, aiming for perioperative mortality below 3%. No drug therapy is evaluated in this review.
A 2015 study of 128 patients with acute intestinal obstruction and enteral insufficiency added hepatoprotective drugs to the treatment scheme and reports a beneficial therapeutic effect on hepatorenal syndrome and enteral insufficiency. The abstract does not name the hepatoprotective drugs, does not give survival or response rates, and does not address chronic intestinal vascular insufficiency specifically. What is still missing: any controlled trial of a vasodilator, pro-angiogenic, or anti-angiogenic drug for chronic intestinal vascular insufficiency; patient stratification by degree of stenosis or collateral capacity; and funding for a prospective study that measures clinically meaningful endpoints such as pain-free walking distance (if claudication is present) or infarction-free survival.
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 Clinical Investigation · 2008 · 86 citations
Angiogenesis in inflammatory bowel disease
AbstractBoth ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel diseases, are recognized, at the moment, as perplexing and challenging clinical entities, in which several molecules and cell types are implicated. Recent molecular evidence proposes the intestinal microvascular remodelling or angiogenesis, as a phenomenon implicated in the pathogenesis of these chronic inflammatory disorders, together with other proposed theories involved in the pathogenesis of inflammatory bowel diseases, such as genetic, microbacterial and immune factors. Intestinal damage is followed by a physiological angiogenesis, but the abnormal expression of pro- and anti-angiogenic molecules and the changes of vascular cell types could reflect a pathological vascular remodelling. Thus, the inflammation may be favoured and maintained by a pathological angiogenesis. A better understanding of the angiogenic process may facilitate the design of more effective therapies for chronic intestinal inflammation.
European Journal of Clinical Investigation · 2005 · 49 citations
Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel disease
AbstractThis review has focused on evidence regarding intestinal perfusion of inflammatory bowel disease (IBD). Basic investigation has defined an altered microvascular anatomy in the affected IBD bowel, which corresponds with diminished mucosal perfusion in the setting of chronic, long-standing inflammation. Diminished perfusion is linked to impaired wound healing, and may contribute to the continued refractory mucosal damage, which characterizes IBD. Alterations in vascular anatomy and physiology in IBD suggests additional possible mechanisms by which micro-vessels may contribute to the initiation and perpetuation of IBD. This begs the following questions: will angiogenesis within the gut lead to sustained inflammation, does the growing vasculature generate factors that transform the surrounding tissue and does angiogenesis generate vascular anastomosis within the gut, with shunting of blood away from the mucosal surface, impairment of metabolism and potentiation of gut damage? Further studies are required to define the mechanisms that underlie the vascular dysfunction and its role in pathophysiology of IBD.
Annals of Surgery · 2001 · 38 citations · open access
Effect of Prolonged Selective Intramesenteric Arterial Vasodilator Therapy on Intestinal Viability After Acute Segmental Mesenteric Vascular Occlusion
AbstractOBJECTIVE: To evaluate the effect of selective intramesenteric artery vasodilator infusion on intestinal viability in a rat model of acute segmental mesenteric vascular occlusion. SUMMARY BACKGROUND DATA: Although intramesenteric arterial vasodilator infusion may be an effective treatment for nonocclusive mesenteric ischemia, it has also been advocated to increase collateral blood flow after mesenteric vascular occlusion. However, the authors have previously found that intraarterial vasodilators actually reduce collateral blood flow acutely, by preferentially dilating the vasculature of adjacent, nonischemic mesenteric vascular beds, a phenomenon well established in other organs. METHODS: A segment of rat ileum was acutely devascularized, with blood flow provided only by collateral arterial vessels from adjacent, nonischemic bowel. Papaverine (30 or 40 microg/kg/min), isoproterenol (0.06 microg/kg/min), norepinephrine (0.1 or 0.2 microg/kg/min), or vehicle saline was continuously infused into the cranial (superior) mesenteric artery for 48 hours. Viability was then assessed using previously established, objective gross and microscopic criteria. RESULTS: Although papaverine increased total mesenteric blood flow in normally vascularized rats, it not only failed to improve but actually significantly reduced the length of the devascularized segment maintained viable by collateral blood flow after 48 hours. Isoproterenol had a similar effect. Norepinephrine infusion decreased both normal mesenteric blood flow and viable segment length. CONCLUSIONS: These findings suggest that intraarterial vasodilator therapy fails to improve intestinal viability after segmental mesenteric vascular occlusion.
Zentralblatt für Chirurgie - Zeitschrift für Allgemeine Viszeral- Thorax- und Gefäßchirurgie · 2011 · 7 citations
Chronisch-progrediente Durchblutungsstörungen der Darmarterien – kompakte Kurzübersicht aus gefäßchirurgischer Perspektive
AbstractBACKGROUND: Intestinal ischaemia is quite rare among the cardiovascular diseases. However, it is increasingly diagnosed. The aim of this selective but representative short overview is to assess the impact of intestinal ischaemia in vascular and visceral medicine from a vascularsurgical perspective. MATERIAL AND METHODS: A literature search and selection in relevant online services of the medical scientific literature was performed, in particular, of the last decade on the competent management of intestinal ischaemia combined with the clinical expertise obtained in daily vascular surgical practice including didactically prepared demonstrable cases / case reports related to typical / specific clinical problems and situations. RESULTS AND DISCUSSION: Although the superior mesenteric artery (SMA) is most frequently responsible for the clinical presentation, usually 2 or 3 major arterial trunks are involved for a relevant clinical symptomatology. These disorders of the intestinal circulation are most frequently caused by progressive atherosclerotic occlusive disease. In chronic progressive disease, the visceral arteries show the ability to enlarge typical collateral circulation pathways, which may not always lead to a complete compensation. With a degree of stenosis of more than 70 %, mesenteric ischaemic pain and physical prostration are the major clinical findings. Intestinal infarction with a mortality rate of 60-80 % is the endpoint of the chronically progressive intestinal ischaemia. There-fore, an urgent medical treatment is highly required. CT angiography is the diagnostic procedure of choice in patients with suspected chronic intestinal ischaemia. Mesenteric angiography is subject to specific questions and / or to endovascular arteriographic treatment. Duplex scanning has been advocated as a non-invasive method of pre- and post-interventional screening. Treatment is indicated in symptomatic intestinal vascular disease. Due to the high morbidity of the majority of patients and the enormous invasivity associated with conventional surgery, arteriographic intervention is the treatment of choice, even though quality improvement is required. Surgical reconstructions are highly standardised and should be associated with perioperative mortality less than 3 %. We recommended the reconstruction of 2 vessels, for which antegrade supracoeliacal revascularisation techniques are favourable. In (threatening) septic conditions, autologous reconstructions are required. Intestinal infarction is the most serious complication of all visceral revascularisations. In recurrent occlusions of visceral arteries, it is recommended to favour and finally use a different therapeutic modality. Post-therapeutic care includes second-look operation as well as clinical examination and diagnostic imaging. Antithrombotic therapy should be initiated. The further screening of patients after intestinal revascularisation should be performed by duplex scanning. CONCLUSION: Chronically progressive occlusive disease of intestinal arteries is considered as a complex disease with challenging diagnostic and therapeutic management, in which an interdisciplinary, partly finding- and stage-dependent (also with regard to the frequency and recurrency of the specific local finding) sequential therapeutic approach (e. g., endovascular vs. open procedure; interventionalist / endovascular specialist / vascular surgeon) becomes more and more relevant requiring a competent center of vascular medicine.
I P Pavlov Russian Medical Biological Herald · 2015 · 0 citations · open access
Severity of hepatic dysfunction and its correction in the complex treatment of acute intestinal obstruction
AbstractThe article describes the role that could play a hepatoprotective therapy in the treatment of patients with acute intestinal obstruction. The study involved 128 patients with mechanical acute intestinal obstruction, accompanied by the syndrome of enteral insufficiency. Hepatoprotective drugs have been added in the scheme of treatment. It has been proven beneficial therapeutic effect of this measure on the dynamics of the development of hepatorenal syndrome, syndrome of enteral insufficiency.
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.
