DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for angioedema — 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 moduleAngioedema 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 angioedema 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
kallikrein B1 (KLKB1) — KLKB1 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 bendrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I44 · 1.36 Å · ligand BENZAMIDINE (BEN). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 review noted that four drugs—plasma-derived C1 inhibitor, recombinant human C1 inhibitor, the kallikrein inhibitor DX-88, and the B2 bradykinin receptor antagonist HOE-140—had each shown efficacy and safety for treating hereditary angioedema in Phase III trials, though no approved therapy existed in the USA at that time. A 2015 review stated that hereditary angioedema management was still evolving, that drug therapy was very costly, and that it was not available worldwide.
In a 2025 Phase III trial (CASPIAN) of lanadelumab for non-histaminergic normal C1 inhibitor angioedema, 77 patients were randomised (50 to lanadelumab, 27 to placebo). The primary endpoint was not met: attacks per month were 1.82 with lanadelumab versus 1.78 with placebo (rate ratio 1.02, p=0.90). Attack rate reduction from baseline occurred in both groups. In a subgroup meeting a clinical definition of hereditary angioedema (known mutations or family history with unknown mutations, n=18), a positive trend in attack rate reduction was seen with lanadelumab. In the open-label extension, attack rate reduction was observed. All treatment-related adverse events were non-serious and mostly non-severe. The authors concluded efficacy remained inconclusive.
A long-term open-label extension of the COMPACT trial examined subcutaneous C1-inhibitor (60 IU/kg twice weekly) in 63 patients with hereditary angioedema. The median reduction in attack rate relative to placebo had been 95% in the pivotal trial, and the median reduction in on-demand medication use had been >99%. In the extension, 35 patients had 371 attacks; 229 (61.7%) were treated with on-demand medication, mostly with intravenous C1-inhibitor (62%) or icatibant (38%). Twenty-eight patients (44.4%) had no attacks, and 39 (61.9%) used no on-demand medication; 66.7% used it less than once per year (mean 3.8 uses/year, median 0.0). Between months 25 and 30, 87% (20/23) used no on-demand medication.
A 2021 case report described venlafaxine-induced angioedema in an older adult, noting that angioedema is a well-documented reaction with ACE inhibitors via the bradykinin pathway. A 2023 case report described a 34-year-old man with hereditary angioedema who had suffered several attacks per month despite prophylactic antifibrinolytics and androgens, and who used plasma-derived C1-INH or icatibant for on-demand treatment. After starting teriflunomide 14 mg/day for multiple sclerosis, his angioedema attacks disappeared 40 days later. The authors stated that teriflunomide’s effectiveness for prophylaxis should be further studied.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Expert Opinion on Investigational Drugs · 2008 · 20 citations
New promise and hope for treating hereditary angioedema
AbstractBACKGROUND: While there is no approved effective therapy for the treatment of acute attacks of hereditary angioedema in the USA, four different drugs are completing or have recently completed Phase III clinical trials. OBJECTIVE: To review the clinical status and future prospects of the new therapies under development for the treatment of hereditary angioedema. METHODS: A review was carried out of the literature and presentations at meetings on the efficacy and safety of plasma-derived C1 inhibitor, recombinant human C1 inhibitor, the kallikrein inhibitor DX-88, and the B2 bradykinin receptor antagonist HOE-140. RESULTS/CONCLUSION: Each of these drugs has been shown to be effective and safe for the treatment of hereditary angioedema; however, subtle differences in their mechanisms of action and delivery may influence how physicians and patients utilize the different drugs. The availability of effective therapy is expected to reshape the management of hereditary angioedema.
Frontiers in Immunology · 2025 · 4 citations · open access
Lanadelumab for prevention of attacks of non-histaminergic normal C1 inhibitor angioedema: results from the randomized, double-blind CASPIAN Study and CASPIAN open-label extension
AbstractBackground: Randomized controlled trial data for non-histaminergic normal C1 inhibitor (nC1INH) angioedema prevention are lacking. Methods: Patients aged ≥12 years with investigator-confirmed non-histaminergic nC1INH angioedema were enrolled in phase III, multicenter, randomized, placebo-controlled, double-blind CASPIAN Study (NCT04206605). Patients with ≥1 investigator-confirmed angioedema attack/4 weeks during observation period were randomized 2:1 to lanadelumab 300 mg every 2 weeks or placebo. Primary efficacy outcome was investigator-confirmed angioedema attack number during the 26-week treatment period. Safety was analyzed as treatment-emergent adverse events (TEAEs). After completing the treatment period, patients could roll over to CASPIAN open-label extension (CASPIAN OLE; NCT04444895) for an additional 26-week lanadelumab treatment to assess long-term safety and efficacy. Results: A total of 77 patients (mean ± SD age of 42.8 ± 12.9 years, 80.5% women, 88.3% White) were enrolled (lanadelumab, 50; placebo, 27). Primary efficacy outcome was not different with lanadelumab versus placebo (1.82 vs. 1.78 attacks/month; rate ratio, 1.02; p=0.90), with attack rate reduction from baseline in both groups. Subgroups meeting a clinical definition of HAE [known mutations (n=5) or family history and unknown mutations (n=13)] showed positive attack rate reduction trend with lanadelumab versus placebo. Angioedema attack rate reduction with lanadelumab was observed in CASPIAN OLE. In both studies, all treatment-related TEAEs were non-serious, and most were non-severe; most frequent treatment-related TEAEs were similar to those previously reported in lanadelumab clinical trials. Conclusion: In patients with non-histaminergic nC1INH angioedema, lanadelumab safety was consistent with previous studies; efficacy remained inconclusive due to unmet CASPIAN primary endpoint. Overall results suggest potential clinical benefit in symptom control. Clinical trial registration: https://www.clinicaltrials.gov/, identifiers NCT04206605, NCT04444895.
SAGE Open Medical Case Reports · 2021 · 3 citations · open access
A case of venlafaxine-induced angioedema in an older adult
AbstractAngioedema is a serious adverse event that can manifest as lower extremity edema, face swelling, rash, hives, and a swollen tongue, which can sometimes lead to airway constriction and death. It is a well-documented reaction within the angiotensin-converting enzyme inhibitor drug class, where the bradykinin pathway leads to angioedema. We report a case where a patient experienced angioedema after taking venlafaxine. We evaluated other antidepressants as potential treatment options for the patient. We further examined potential cross-reactivity between antidepressants in order to find alternative medications for patients that experience serious adverse effects.
Hereditary Angioedema : A Literature Review and National Management Guidelines
AbstractBACKGROUND: Hereditary angioedema, a rare and potentially life-threatening condition, is the result of a defect in the C1 esterase inhibitor. Primary care physicians should be familiar with this condition to avoid complications and improve quality of care. METHODS: We present two cases of hereditary angioedema followed by a discussion based on a literature review of the recent guidelines and advances in this condition. OBJECTIVES: To highlight the clinical aspects, diagnosis and treatment of this condition and propose a practical local management based on the available medication. CONCLUSION: Hereditary angioedema management is still evolving. More efforts should be made concerning the drug therapy which is very costly and not available worldwide.
Journal of Drug Assessment · 2019 · 1 citations · open access
Patterns of on-demand medication use in patients with hereditary angioedema treated long-term with prophylactic subcutaneous C1-inhibitor
AbstractBackground: Hereditary angioedema (HAE) is characterized by recurrent, debilitating attacks of angioedema that may require immediate (on-demand) treatment. HAE prophylactic therapy may reduce the need for on-demand treatment by decreasing the frequency and severity of attacks, which may in turn impact treatment costs. Subcutaneous C1-inhibitor (C1-INH [SC], HAEGARDA®, CSL Behring) at the FDA-approved dose of 60 IU/kg is indicated as routine prophylaxis to prevent attacks in patients with HAE. In the pivotal phase III COMPACT trial, the median reduction in attack rate relative to placebo was 95% with twice-weekly C1-INH (SC) 60 IU/kg, and the median reduction in on-demand medication use was >99%. Aims: We examined patterns of on-demand medication use in patients treated with C1-INH (SC) 60 IU/kg in a long-term, open-label extension (OLE) of the COMPACT trial. Methods: The OLE of the COMPACT trial was a multicenter, international, randomized, parallel-arm study that evaluated patients aged ≥6 years with ≥4 attacks over 2 consecutive months before enrollment. The trial included patients from the COMPACT trial and C1-INH (SC)-naïve patients. Patients were randomized to receive C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 weeks or up to 140 weeks (US patients only). The time-normalized number of uses of medication for treatment of HAE attacks was an exploratory endpoint. Results: Of the 63 patients in the 60 IU/kg group, 35 had a total of 371 attacks, of which 229 (61.7%) were treated with on-demand medication: 84% (192/229) were treated with 1 medication, 62% with C1-INH (IV), and 38% with icatibant. The majority of treated attacks (113/229) were severe. A total of 28 patients (44.4%) had no attacks, 11 (17.5%) had no treated attacks, and 24 (38.1%) had ≥1 treated attack. Post-hoc analysis of annualized on-demand medication use showed that 39 patients (61.9%) treated with C1-INH (SC) 60 IU/kg did not use any on-demand medication; 66.7% used it less than once per year (mean (SD): 3.8 (9.6) uses/year; median: 0.0 uses/year). Between months 25 and 30, 87% of patients (20/23) did not use any on-demand medication (mean: 0.08/month, or ∼1 use/year). Conclusions: On-demand medication use remained consistently low during prophylactic therapy with C1-INH (SC) in the OLE study, with two-thirds of patients using medication less than once per year. Reduction in on-demand medication use over time should be considered in cost-effectiveness analyses of HAE prophylactic therapies.
European Journal of Case Reports in Internal Medicine · 2023 · 0 citations · open access
Remission of hereditary angioedema attacks associated with starting teriflunomide in a patient with multiple sclerosis
AbstractBackground: Hereditary angioedema is a rare hereditary and potentially life-threatening disorder characterized by recurrent attacks of cutaneous and submucosal swelling. In spite of the advances made in terms of pathophysiology, underlying mechanisms are not fully clear and this, in turn, hinders the development of effective therapies. Currently, on demand treatment is considered first-class, with few cost-effective, long-term prophylactic options. Case presentation: Here we describe the case of a 34-year-old man diagnosed with hereditary angioedema at the age of 10, who used to suffer several angioedema attacks per month. He was given prophylactic treatment with antifibrinolytic agents and androgens without improvement. Moreover, he was treated with plasma-derived C1-INH concentrate or icatibant for on-demand treatment of moderate and severe angioedema attacks. At the age of 33, after suffering sudden vision loss and lower limb paresthesia, he was studied and diagnosed with multiple sclerosis. Teriflunomide was administered at a dosage of 14 mg/day. Angioedema attacks disappeared 40 days after starting treatment. Conclusion: Thus, we suggest considering the pathophysiologic mechanisms on which teriflunomide could be active and consider this drug carefully as an option for prophylaxis purposes. Yet, its effectiveness on this condition should be further studied. LEARNING POINTS: Underlying mechanisms in hereditary angioedema lack clarity and hence hinder the development of effective therapies.On-demand treatment of hereditary angioedema is considered first class, with few cost-effective, long-term prophylactic options.The mechanisms of action and effectiveness of teriflunomide on hereditary angioedema should be studied further.
Expert Review of Clinical Immunology · 2008 · 0 citations · open access
Pameran, Lelong Barang Antik Di Muzium Sultan Alam Shah
AbstractCinryze is a pasteurized, nanofiltered plasma derived concentrate of C1-inhibitor (pdC1-INH) licensed for the prophylactic treatment of hereditary angioedema. In a double-blind placebo-controlled crossover trial to evaluate Cinryze as prophylaxis, the frequency of attacks was halved (6.26 per 12 weeks on Cinryze versus 12.73 per 12 weeks on placebo). Furthermore, attacks were generally milder and of shorter duration. For treatment of acute attacks in patients receiving Cinryze, 1000 units, within 4 h of the start of an attack, the estimated time to the onset of unequivocal relief was reduced to 2 h, compared with more than 4 h in those treated with placebo. Cinryze and other similar products are going to change the future management of hereditary angioedema and have potential in other areas of medicine.
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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