DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Darier 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 moduleDarier 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 darier 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 sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2) — ATP2A2 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.
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RCSB Protein Data Bank · entry 6LLY · 2.8 Å · ligand BERYLLIUM TRIFLUORIDE ION (BEF). Experimental structure, not a prediction.
What the evidence adds up to
In 1997, four new cases of localised Darier disease were reported and the English-language literature was reviewed. The average age at onset was 27 years, the trunk was the most frequent site of involvement (40% of 40 cases), and sunlight, heat or sweating aggravated the condition in 42% of reported cases. Topical tretinoin produced a response in 38% of patients. The authors concluded that localised Darier disease is probably a genetic mosaic of the generalised form.
A 2021 review argues that Darier disease should be considered a systemic condition, not merely a skin disorder, because the mutated ATP2A2 gene encodes a calcium pump expressed in most tissues. The review calls for systemic, disease-mechanism-targeted treatments but does not report any clinical trial results or specific drug outcomes.
A 2015 Swedish nationwide matched cohort study of 770 individuals with Darier disease found a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1–12.4). Among conscripted individuals with Darier disease who had no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than in matched comparison subjects. The authors state that Darier-causing mutations merit further attention in molecular genetic research on intellectual disability.
No randomised controlled trials of any systemic drug for Darier disease are reported in these abstracts. What is missing is a properly funded, placebo-controlled trial that stratifies patients by genotype and measures both skin and cognitive outcomes over a sufficient period.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Dermatology · 1997 · 71 citations
Localized Darier Disease
AbstractBACKGROUND: Darier disease is an uncommon genodermatosis characterized by the symmetrical eruption of keratotic reddish-brown papules occurring in the seborrheic areas of the body. A unilateral, or localized, variant has been identified. We report 4 new cases of localized Darier disease and review the English-language literature. The implications of these cases on future genetic studies are also discussed. OBSERVATIONS: Localized Darier disease occurred with equal frequency in males and females. The average age at onset was 27 years. The most frequent site of involvement was the trunk (40% [16/40]). This condition was aggravated by sunlight, heat, or sweating in 42% (19/40) of reported cases, and 38% (15/40) of the patients responded to treatment with topical tretinoin. CONCLUSIONS: Many of the clinical features of localized Darier disease suggest that it is a genetic mosaic of generalized Darier disease. Further studies of localized Darier disease may therefore prove to be instrumental in the search for the Darier disease gene.
AbstractDarier disease is a severe, rare autosomal dominant inherited skin condition caused by mutations in the ATP2A2 gene encoding sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 in the endoplasmic reticulum. Since sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 is expressed in most tissues, and intracellular calcium homeostasis is of fundamental importance, it is conceivable that other organs besides the skin may be involved in Darier disease. This review focusses on the association of Darier disease with other organ dysfunctions and diseases, emphasizing their common molecular pathology. In conclusion, Darier disease should be considered a systemic condition that requires systemic and disease mechanism targeted treatments.
British Journal of Dermatology · 2015 · 30 citations
Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study
AbstractBACKGROUND: Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations. OBJECTIVES: To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease. METHODS: We conducted a matched cohort study based on Swedish Population-, Patient- and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability. RESULTS: Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1-12.4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects. CONCLUSIONS: Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability.
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.
