DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Hailey-Hailey disease — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHailey-Hailey disease maps to a 1-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 hailey-hailey disease 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
ATPase secretory pathway Ca2+ transporting 1 (ATP2C1) — ATP2C1 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 acpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7YAG · 3.1 Å · ligand PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER (ACP). Experimental structure, not a prediction.
What the evidence adds up to
A 2005 journal article titled "Hailey-Hailey disease failing to respond to treatment" exists but provides no patient data, outcomes, or specific therapies in its abstract; it simply documents that treatment failure occurs. A 2002 case describes one patient whose initial presentation mimicked erythema multiforme or toxic epidermal necrolysis, and the authors suggest bacterial infection may have worsened the acantholysis. No treatment or outcome is reported for that case.
A 2014 case report describes a 45-year-old woman with generalised Hailey-Hailey disease and a novel splice-site mutation in ATP2C1 whose condition "dramatically improved and was well controlled" by narrow-band UVB phototherapy. A 2017 case of psoriasiform Hailey-Hailey disease in a 60-year-old woman was "successfully treated" with twice-daily doxycycline, mometasone, and clindamycin. A 2019 review mentions Castellani paint as a management option but provides no patient numbers or response data. A 2022 case reports a 69-year-old woman whose skin lesions regressed after methotrexate was introduced for rheumatoid arthritis, with "significant impact" on quality of life; she had previously failed topical and oral corticosteroids, tetracyclines, antifungals, and azathioprine.
A 2024 report describes two patients with long-standing, treatment-resistant Hailey-Hailey disease who experienced "significant symptom relief" from a combination of oral naltrexone and dupilumab injections. The authors highlight targeting the Th2 pathway and calcium signalling, and note that Th2 blockade with dupilumab plus naltrexone "effectively controls recalcitrant HHD." All of these are single cases or two-patient reports. No controlled trials, no randomised comparisons, no consistent outcome measures, and no long-term follow-up data are provided in any of these abstracts. What is still missing is any prospective trial with adequate sample size, standardised severity scoring, and a control arm; without that, the evidence remains anecdotal and cannot guide treatment decisions.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical and Experimental Dermatology · 2002 · 28 citations
Acute generalized Hailey-Hailey disease
AbstractA patient with extensive histologically proven Hailey-Hailey disease is described whose initial clinical presentation was suggestive of erythema multiforme or toxic epidermal necrolysis. This potentially misleading morphology of acute proven Hailey-Hailey disease has not been described previously and may be a consequence of bacterial infection exacerbating acantholysis.
Successful treatment with narrow-band UVB therapy for a case of generalized Hailey-Hailey disease with a novel splice-site mutation in<i>ATP</i><i>2</i><i>C</i><i>1</i>gene
AbstractHailey-Hailey disease (HHD) is a rare autosomal dominant disorder characterized by development of recurrent blisters, erosions, and crustations in the intertriginous areas. The treatment of HHD is often challenging, and various methods have been tried. We report here a case of a 45-year-old woman with a generalized form of HHD that was dramatically improved and well controlled by narrow-band ultraviolet B phototherapy.
Treatment of Recalcitrant Hailey-Hailey Disease With Naltrexone and Dupilumab: A Report of Two Cases
AbstractThis report presents two cases of patients with long-standing, treatment-resistant Hailey-Hailey disease (HHD) who experienced significant symptom relief through a combination therapy of oral naltrexone and dupilumab injections. The therapeutic potential of targeting the Th2 pathway and Ca2+ signaling with dupilumab in managing HHD manifestations is highlighted. The findings suggest that Th2 blockade with dupilumab, in conjunction with naltrexone, effectively controls recalcitrant HHD, indicating a role of cytokine response in altering disease pathogenesis. This case contributes to the growing body of literature on biologic treatments for HHD and suggests avenues for further research in HHD management.
Clinical and Experimental Dermatology · 2005 · 7 citations
Hailey-Hailey disease failing to respond to treatment
AbstractJournal Article Hailey–Hailey disease failing to respond to treatment Get access R. K. H. Mak, R. K. H. Mak St. John's Institute of Dermatology, Guys' and St Thomas' Hospital, London SE1 7EH, UK Email: [email protected] Search for other works by this author on: Oxford Academic Google Scholar S. M. B. Reynaert, S. M. B. Reynaert St. John's Institute of Dermatology, Guys' and St Thomas' Hospital, London SE1 7EH, UK Email: [email protected] Search for other works by this author on: Oxford Academic Google Scholar N. Agar, N. Agar St. John's Institute of Dermatology, Guys' and St Thomas' Hospital, London SE1 7EH, UK Email: [email protected] Search for other works by this author on: Oxford Academic Google Scholar M. M. Black M. M. Black St. John's Institute of Dermatology, Guys' and St Thomas' Hospital, London SE1 7EH, UK Email: [email protected] Search for other works by this author on: Oxford Academic Google Scholar Clinical and Experimental Dermatology, Volume 30, Issue 5, 1 September 2005, Pages 598–599, https://doi.org/10.1111/j.1365-2230.2005.01830.x Published: 01 September 2005 Article history Accepted: 18 February 2005 Published: 01 September 2005
JAAD Case Reports · 2019 · 5 citations · open access
Management of Hailey-Hailey disease with Castellani paint
AbstractHailey-Hailey disease (HHD), also called familial benign chronic pemphigus, is a rare genodermatosis first described by the Hailey brothers in 1939.1 HHD is an autosomal-dominant keratinocyte adhesion disorder secondary to loss of function mutations of the ATP2C1 gene, an ATPase responsible for calcium homeostasis.2 HHD manifests as chronic and recurrent red plaques involving intertriginous sites. Affected areas develop painful vesicles, erosions, fissures, and maceration and often have bacterial, fungal, or viral superinfection.
International Journal of Rheumatic Diseases · 2022 · 3 citations · open access
Rheumatoid arthritis and <scp>Hailey‐Hailey</scp> disease treated with methotrexate
AbstractWe report a rare case of long-standing Hailey-Hailey disease in a Caucasian Portuguese 69-year-old woman, recently diagnosed with rheumatoid arthritis. The patient's skin lesions remained active and exudative despite topical and oral treatments with corticosteroids, tetracyclines, antifungals, and oral treatment with azathioprine. After introduction of methotrexate for rheumatoid arthritis treatment, the skin lesions regressed, with significant impact on the patient's quality of life. This case report supports the clinical evidence of methotrexate's potential role in Hailey-Hailey disease treatment.
Psoriasiform Hailey-Hailey Disease Presenting as Erythematous Psoriasiform Plaques Throughout the Body: A Case Report
AbstractINTRODUCTION: Hailey-Hailey disease is an adult-onset skin condition characterized by lesions in the intertriginous regions of the body. The lesions can be pruritic, painful, and associated with physical and social impairment. CASE PRESENTATION: We present a case of psoriasiform Hailey-Hailey disease in a 60-year-old white woman who exhibited erythematous psoriasiform plaques in many areas of her body. The patient's condition was successfully treated with a twice-daily regimen of doxycycline, mometasone, and clindamycin. DISCUSSION: It is important to recognize this variant of Hailey-Hailey disease so it can be diagnosed and treated promptly. Hailey-Hailey disease can be treated with topical corticosteroids and antibiotics and usually is associated with a positive prognosis.
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.
