DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for hidradenitis — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHidradenitis maps to a 35-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 hidradenitis 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
caprin family member 2 (CAPRIN2) — CAPRIN2 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 flcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4OUM · 1.491 Å · ligand CITRATE ANION (FLC). Experimental structure, not a prediction.
What the evidence adds up to
Hidradenitis suppurativa is a chronic or relapsing inflammatory skin disorder of unknown cause, characterised by abscess-like nodules, fistulas, and scarring. Neutrophils are the predominant leukocyte infiltrate in lesions. Immunofluorescence microscopy of HS lesions detected the prominent presence of neutrophil extracellular traps (NETs), and NET complexes correlated with disease severity as measured by Hurley staging. Neutrophils from the peripheral blood of HS patients displayed enhanced spontaneous NET formation compared to healthy control neutrophils. Sera from patients recognised antigens present in NETs and harboured increased antibodies reactive to citrullinated peptides. B cell dysregulation, evidenced by elevated plasma cells and IgG, was observed in both circulation and skin. Peptidylarginine deiminases 1 to 4, enzymes involved in citrullination, were differentially expressed in HS skin in association with enhanced tissue citrullination. NETs in HS skin coexisted with plasmacytoid dendritic cells in association with a type I interferon gene signature.
Current understanding of pathogenesis also suggests hyperkeratosis of the infundibulum leading to follicular occlusion of the pilosebaceous unit plays a role. Bacterial infection with staphylococci, Escherichia coli, and streptococcus is considered a secondary event. Smoking and obesity are known risk factors associated with more severe disease. More recent attention has focused on a possible defect in hair follicle immunity. The exact pathogenic mechanisms remain incompletely understood, and efficient therapies are still lacking.
Treatments are chosen on the basis of disease severity and the existence of associated risk factors or comorbidities. Management has three levels: topical options, systemic options, and surgical methods including laser therapy. Therapies are generally effective against microorganisms, inflammation, or infundibular hyperkeratosis. Where antimicrobial therapy is used, the drugs often have significant additional immunomodulatory effects. Use of simple incisions as treatment is strongly discouraged.
What is still missing is a complete understanding of the pathogenic mechanisms, which prevents the development of targeted therapies. Additional pathogenic as well as therapeutic studies are necessary. No trial has yet tested a drug that specifically blocks NET formation, B cell dysregulation, or the type I interferon pathway in HS patients, and no patient stratification strategy based on these immune markers has been validated in a clinical trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science Translational Medicine · 2019 · 173 citations · open access
Neutrophil extracellular traps, B cells, and type I interferons contribute to immune dysregulation in hidradenitis suppurativa
AbstractHidradenitis suppurativa (HS), also known as acne inversa, is an incapacitating skin disorder of unknown etiology manifested as abscess-like nodules and boils resulting in fistulas and tissue scarring as it progresses. Given that neutrophils are the predominant leukocyte infiltrate in HS lesions, the role of neutrophil extracellular traps (NETs) in the induction of local and systemic immune dysregulation in this disease was examined. Immunofluorescence microscopy was performed in HS lesions and detected the prominent presence of NETs. NET complexes correlated with disease severity, as measured by Hurley staging. Neutrophils from the peripheral blood of patients with HS peripheral also displayed enhanced spontaneous NET formation when compared to healthy control neutrophils. Sera from patients recognized antigens present in NETs and harbored increased antibodies reactive to citrullinated peptides. B cell dysregulation, as evidenced by elevated plasma cells and IgG, was observed in the circulation and skin from patients with HS. Peptidylarginine deiminases (PADs) 1 to 4, enzymes involved in citrullination, were differentially expressed in HS skin, when compared to controls, in association with enhanced tissue citrullination. NETs in HS skin coexisted with plasmacytoid dendritic cells, in association with a type I interferon (IFN) gene signature. Enhanced NET formation and immune responses to neutrophil and NET-related antigens may promote immune dysregulation and contribute to inflammation. This, along with evidence of up-regulation of the type I IFN pathway in HS skin, suggests that the innate immune system may play important pathogenic roles in this disease.
Current Opinion in Infectious Diseases · 2010 · 86 citations
Hidradenitis suppurativa: a review of cause and treatment
AbstractPURPOSE OF REVIEW: Hidradenitis suppurativa is a chronic or relapsing inflammatory cutaneous disorder manifested by recurrent formation of abscesses, fistulating sinus and scarring in the apocrine-gland-bearing skin. This review discusses the different aetiological theories and management opportunities. RECENT FINDINGS: Current understanding of the pathogenesis suggests that hyperkeratosis of the infundibulum, leading to follicular occlusion of the pilosebaceous unit plays a role. Bacterial infection with staphylococci, Escherichia coli and streptococcus is considered as a secondary event in the pathogenesis. Smoking and obesity are both known as risk factors and are associated with more severe disease course. Recently, more attention has been put into the understanding of the immunopathology of the skin and the results indicate that hidradenitis suppurativa may be considered as an inflammatory disease of unknown cause based on a defect in the hair follicle immunity. The treatments are most appropriately chosen on the basis of disease severity and the existence of any associated risk factors or comorbidities. There are three levels in the management of hidradenitis suppurativa: topical options, systemic options and surgical methods including laser therapy. At each level several treatment principles have shown themselves to be efficient, and may therefore be used either alone or in combination. Therapies are generally effective against microorganisms, inflammation or infundibular hyperkeratosis. Where an antimicrobial therapy is used, the drugs used often have significant additional immunomodulatory effects. SUMMARY: The recent studies give us a better insight into the pathogenesis of hidradenitis suppurativa and should translate into improved therapies.
Frontiers in Medicine · 2020 · 80 citations · open access
Hidradenitis Suppurativa: Current Understanding of Pathogenic Mechanisms and Suggestion for Treatment Algorithm
AbstractHidradenitis suppurativa is one of the most distressing dermatological conditions and has a significant negative impact on patients' quality of life. However, the exact pathogenic mechanisms remain incompletely understood and-therefore-efficient therapies are still lacking. The current manuscript focuses on new findings on its pathogenic mechanisms and aims to provide practical therapy recommendations.
Journal of Cutaneous Medicine and Surgery · 2002 · 42 citations
Hidradenitis Suppurativa
AbstractBACKGROUND: Hidradenitis suppurativa is a clinically defined disease that causes considerable morbidity for patients. The results of recent studies, which have increased the understanding of this disease, are reviewed. OBJECTIVE: The epidemiology, risk factors, pathogenesis, and treatment of this disease are summarized to help clinicians with practical patient management. CONCLUSION: Hidradenitis suppurativa remains a clinical challenge to patients and physicians alike. Physicians should be familiar with the impact this disease has on the patient and with the range of treatments available. Use of simple incisions as treatment is strongly discouraged. Additional pathogenic as well as therapeutic studies are necessary.
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.
