DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Dowling-Degos disease — 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 moduleDowling-Degos disease 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 dowling-degos 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
protein O-glucosyltransferase 1 (POGLUT1) — POGLUT1 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 udpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5L0V · 1.305 Å · ligand URIDINE-5'-DIPHOSPHATE (UDP). Experimental structure, not a prediction.
What the evidence adds up to
Dowling-Degos disease is an autosomal dominant genodermatosis characterised by reticular pigmented anomaly mainly affecting flexures. A 1998 study of a large kindred traced through four generations found 50% of members affected, with reticulate acropigmentation of Kitamura and acropigmentation of Dohi overlapping with features of Dowling-Degos disease, and noted autosomal dominant inheritance with variable penetrance. A 2014 Chinese family study in which KRT5 mutation was absent identified a novel 1-bp deletion in POFUT1 by genome-wide linkage and exome sequencing, but this deletion was not found in a second DDD family or a sporadic case, confirming genetic heterogeneity. By 2024, mutations in KRT5, POFUT1, POGLUT1, and PSENEN were considered the primary causes.
A 2022 report discussed a case across three generations and noted associations including hidradenitis suppurativa, along with multiple phenotypic expressions. A 2025 case report described a 61-year-old man with a 20-year history of generalised DDD and refractory pruritus. Oral acitretin 20 mg/day combined with prednisone 20 mg/day for one month exacerbated the pruritus. After switching to tofacitinib 5 mg twice daily, pruritus improved from a baseline Numerical Rating Scale score of 9 to 5–6 within one month; at four-month follow-up, scores stabilised at 2–3, with lesion darkening and no recurrence. No adverse events were reported. The authors called tofacitinib a promising therapeutic option for DDD with refractory pruritus.
The evidence base remains limited to small case series and single case reports. No controlled trials exist. The genetic heterogeneity means that a single drug target is unlikely to address all cases. What is missing is prospective, controlled studies with standardised outcome measures, larger sample sizes, and stratification by genetic mutation type.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Dermatology · 1998 · 50 citations
Overlap of Reticulate Acropigmentation of Kitamura, Acropigmentation of Dohi and Dowling-Degos Disease in Four Generations
AbstractA large kindred is being reported in which reticulate acropigmentation of Kitamura (RAPK) and acropigmentation of Dohi (APD) were associated with features of Dowling-Degos disease (DDD). The pedigree was traced through four generations and 50% of the members were found to be affected. RAPK, APD and DDD are inherited as an autosomal dominant trait with variable penetrance. The differentiation and overlap/association of RAPK, APD and DDD is discussed.
Analysis of POFUT1 Gene Mutation in a Chinese Family with Dowling-Degos Disease
AbstractDowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmented anomaly mainly affecting flexures. Though KRT5 has been identified to be the causal gene of DDD, the heterogeneity of this disease was displayed: for example, POFUT1 and POGLUT1 were recently identified and confirmed to be additional pathogenic genes of DDD. To identify other DDD causative genes, we performed genome-wide linkage and exome sequencing analyses in a multiplex Chinese DDD family, in which the KRT5 mutation was absent. Only a novel 1-bp deletion (c.246+5delG) in POFUT1 was found. No other novel mutation or this deletion was detected in POFUT1 in a second DDD family and a sporadic DDD case by Sanger Sequencing. The result shows the genetic-heterogeneity and complexity of DDD and will contribute to the further understanding of DDD genotype/phenotype correlations and to the pathogenesis of this disease.
Dowling-Degos disease: An association with hidradenitis suppurativa
AbstractDowling-Degos disease is one of the genodermatoses presenting with acquired reticulate pigmentation of the flexures, black-dot papules, and pitted scars. Numerous associated conditions and multiple variants of the disease have been reported in the literature. Several gene mutations play a role in the pathogenesis of the disease giving rise to multiple phenotypic expressions. Herein, we discuss a case in three generations of a family affected with the disease and shed light on the associations and various expressions of the disease.
Oral tofacitinib for generalized Dowling-Degos disease with refractory pruritus: a case report
AbstractTo evaluate the efficacy and safety of the Janus kinase (JAK) inhibitor tofacitinib in generalized Dowling-Degos disease (DDD) with refractory pruritus and to comparatively analyze its advantages and limitations versus existing therapies. We report a 61-year-old male with a 20-year history of generalized DDD presenting with pruritic erythematous-to-brown papules and macules refractory to conventional therapies. Multimodal diagnostic evaluations, including dermoscopy and histopathology confirmed the diagnosis, with pruritus severity quantified using the Numerical Rating Scale (NRS). The patient was initially treated with oral acitretin (20 mg/day) combined with prednisone (20 mg/day) for 1 month, followed by maintenance monotherapy with tofacitinib (5 mg twice daily). Oral acitretin exacerbated the pruritus. Following transition to tofacitinib, pruritus was improved from a baseline NRS score of 9 to 5–6 within 1 month. At four-month follow-up, pruritus scores further stabilized at 2–3, accompanied by lesion darkening without recurrence. No adverse events occurred. Tofacitinib represents a promising therapeutic option for DDD with refractory pruritus.
Journal of Medical Society · 2024 · 0 citations · open access
Exploring unusual cutaneous manifestations in Dowling–Degos disease: A rare case report
AbstractDowling Degos Disease (DDD) is also referred to as post-pubertal reticulate hyperpigmentation or reticular pigmented anomaly of the flexures. It is an extremely uncommon disorder that typically manifests as reticulate hyperpigmentation of the flexures, comedo-like follicular papules, and pitted perioral scars. Dowling and Freudenthal published the first literary description of it in 1938, and Jones and Grice classified it clinically and histopathologically in 1978. It is an uncommon autosomal dominant genodermatosis, and it often manifests after puberty, more especially in adults. Mutations in the genes KRT5, POFUT1, POGLUT1, and most recently PSENEN are thought to be the primary cause of DDD.
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.
