DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Pyoderma — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePyoderma maps to a 3-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 pyoderma 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
interleukin 1 beta (IL1B) — IL1B 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5R8Q · 1.23 Å · ligand 1-methyl-N-{[(2S)-oxolan-2-yl]methyl}-1H-pyrazole-3-carboxamide (JGY). Experimental structure, not a prediction.
What the evidence adds up to
Pyoderma gangraenosum is an extra-intestinal manifestation of chronic inflammatory bowel disease. In multivariate analyses it was significantly and independently associated with black African origin, family history of ulcerative colitis, uninterrupted pancolitis as the initial location of inflammatory bowel disease, permanent stoma, eye involvement and erythema nodosum. The treatment of choice for idiopathic pyoderma gangraenosum is systemic corticosteroids, with cyclosporine A, mycophenolate mofetil and tumour necrosis factor-alpha inhibitors used as second-line or adjuvant options. Small studies have reported successful intervention with alefacept, visilizumab or anakinra, but controlled trials are warranted. Topical tacrolimus has been used off-label in localised disease. No controlled trial data are provided for any of these drugs.
A 2012 study investigated the molecular link between scabies mite infestation and secondary bacterial pyoderma caused by Streptococcus pyogenes. Six purified recombinant scabies mite complement inhibitor proteins, tested at 50 µg/ml, blocked all three complement activation pathways in ELISA-based assays. In human whole blood assays, four of these mite proteins increased Streptococcus pyogenes survival rates by 2- to 15-fold. The authors propose that local complement inhibition in scabies-infested skin promotes bacterial survival and the development of pyoderma.
A 2012 New Zealand survey of companion animal veterinarians reported on antimicrobial use for 1,799 cases of presumptive bacterial infections. For 359 cases of canine superficial pyoderma, 44% were treated with amoxicillin-clavulanic acid and 43% with cephalexin, with median reported treatment durations of 7 and 10 days respectively. Culture and susceptibility testing had been used in only 19% of all reported cases. The authors note that many cases of superficial pyoderma were treated for less than the recommended 21 days, which may contribute to recurrent pyoderma and drug resistance. Fluoroquinolones and amoxicillin-clavulanic acid, considered critically important for human health, were frequently prescribed without culture testing.
What is missing for pyoderma gangraenosum are controlled trials for the newer drugs mentioned, and for canine pyoderma, consistent adherence to recommended treatment durations and routine culture-guided antibiotic selection. The scabies-mite complement inhibitor work remains at the preclinical stage, with no human trial data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Rheumatology · 2010 · 76 citations
Pyoderma gangraenosum
AbstractPURPOSE OF REVIEW: To describe current progress in understanding pyoderma gangraenosum, illustrate clinical observations and discuss therapeutic interventions. RECENT FINDINGS: The proline-rich, glutamic acid-rich, serine-rich and threonine-rich (PEST) family of protein tyrosine phosphatases is a critical regulator of adhesion and migration. PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. This pathway seems to be involved in diseases related to pyoderma gangraenosum such as chronic inflammatory bowel disease and aseptic abscesses syndrome. Pyoderma gangraenosum is one of the most common extra-intestinal manifestations of chronic inflammatory bowel disease. In multivariate analyses, pyoderma gangraenosum was significantly and independently associated with black African origin, familial history of ulcerative colitis, uninterrupted pancolitis as the initial location of inflammatory bowel disease, permanent stoma, eye involvement and erythema nodosum. The treatment of choice for idiopathic pyoderma gangraenosum is systemic corticosteroids but cyclosporine A, mycophenolate mofetil and tumour necrosis factor-alpha inhibitors have been successful to control pyoderma gangraenosum as second line or adjuvant options. In addition, small studies have been published with successful therapeutic intervention using alefacept, visilizumab or anakinra but controlled trials are warranted. Although systemic immunosuppressants remain the choice therapy for most cases of pyoderma gangraenosum, a local approach should be considered in localized disease. Recently, topical tacrolimus has successfully been used as an off-label drug in localized disease. SUMMARY: By a better understanding of the underlying pathology and recent drug developments patients with pyoderma gangraenosum will benefit. For several new drugs, however, controlled trials are warranted.
Complement Inhibitors from Scabies Mites Promote Streptococcal Growth – A Novel Mechanism in Infected Epidermis?
AbstractBACKGROUND: Scabies is highly prevalent in socially disadvantaged communities such as indigenous populations and in developing countries. Generalized itching causes discomfort to the patient; however, serious complications can occur as a result of secondary bacterial pyoderma, commonly caused by Streptococcus pyogenes (GAS) or Staphylococcus aureus. In the tropics, skin damage due to scabies mite infestations has been postulated to be an important link in the pathogenesis of disease associated with acute rheumatic fever and heart disease, poststreptococcal glomerulonephritis and systemic sepsis. Treatment of scabies decreases the prevalence of infections by bacteria. This study aims to identify the molecular mechanisms underlying the link between scabies and GAS infections. METHODOLOGY/PRINCIPAL FINDINGS: GAS bacteria were pre-incubated with blood containing active complement, phagocytes and antibodies against the bacteria, and subsequently tested for viability by plate counts. Initial experiments were done with serum from an individual previously exposed to GAS with naturally acquired anti-GAS antibodies. The protocol was optimized for large-scale testing of low-opsonic whole blood from non-exposed human donors by supplementing with a standard dose of heat inactivated human sera previously exposed to GAS. This allowed an extension of the dataset to two additional donors and four proteins tested at a range of concentrations. Shown first is the effect of scabies mite complement inhibitors on human complement using ELISA-based complement activation assays. Six purified recombinant mite proteins tested at a concentration of 50 µg/ml blocked all three complement activation pathways. Further we demonstrate in human whole blood assays that each of four scabies mite complement inhibitors tested increased GAS survival rates by 2-15 fold. CONCLUSIONS/SIGNIFICANCE: We propose that local complement inhibition plays an important role in the development of pyoderma in scabies infested skin. This molecular link between scabies and bacterial infections may provide new avenues to develop alternative treatment options against this neglected disease.
New Zealand Veterinary Journal · 2012 · 42 citations
Descriptive epidemiological study of the use of antimicrobial drugs by companion animal veterinarians in New Zealand
AbstractAIM: To describe the patterns of use of antimicrobial drugs by veterinary surgeons treating commonly presented bacterial infections in companion animals in New Zealand. METHODS: A postal survey of 800 randomly selected companion animal veterinarians practicing in New Zealand was conducted between August and December 2008. Data were collected regarding the antimicrobials prescribed for recent cases of skin, ear and urinary tract infections; the use of culture and susceptibility testing; and veterinarian characteristics such as proportion of time spent treating companion animals and recent attendance at continuing professional development (CPD) events. Potential associations within the data were explored using extended mosaic plots and multivariable regression models. RESULTS: Completed surveys from 393 respondents were available for analysis, providing data on systemic antimicrobial drug use for 1,799 cases of presumptive bacterial infections. The most frequently prescribed drugs were amoxicillin-clavulanic acid (864 cases, 48%), cephalexin (558, 31%), and fluoroquinolones (198, 11%). Of 359 cases of canine superficial pyoderma, 157 (44%) were treated with amoxicillin-clavulanic acid and 155 (43%) were treated with cephalexin with median reported treatment durations of 7 and 10 days, for these two drugs respectively. Culture and susceptibility tests had been used in 376 of 1,984 (19%) of all reported cases and 160 (43%) of these were suspected urinary tract infections. Practitioners that spent 100% of their time treating companion animals and who had attended a CPD course related to companion animals within the 12 months prior to completing the survey were more likely to submit a sample for culture and susceptibility testing and to prescribe longer courses of antimicrobials for the treatment of canine pyoderma than practitioners who spent less than 100% of their time treating companion animals and had not attended a CPD course in the last 12 months. CONCLUSIONS: Broad-spectrum drugs considered by the World Health Organisation to be critically important for human health, such as fluoroquinolones and amoxicillin-clavulanic acid, are amongst the most frequently prescribed antimicrobials in companion animal medicine, and these drugs are often prescribed without submitting a sample for culture and susceptibility testing. CLINICAL RELEVANCE: Many cases of superficial pyoderma were treated for less than the recommended duration of 21 days, which may contribute to a higher rate of recurrent pyoderma and the development of drug resistance within the causal bacteria. Veterinarians should be aware that the use of fluoroquinolones, in particular, should be based upon the results of a culture and susceptibility test.
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.
