DeCure for Palmoplantar keratoderma, epidermolytic
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for palmoplantar keratoderma, epidermolytic — 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 modulePalmoplantar keratoderma, epidermolytic 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 palmoplantar keratoderma, epidermolytic 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
keratin 1 (KRT1) — KRT1 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…
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RCSB Protein Data Bank · entry 6UUI · 2.069 Å · ligand octyl beta-D-glucopyranoside (BOG). Experimental structure, not a prediction.
What the evidence adds up to
One 2015 case report describes a patient with refractory palmoplantar keratoderma who was treated with alitretinoin. The abstract does not give the sample size, the specific subtype of keratoderma, or any quantitative outcomes such as response rates or survival. No controlled data are provided.
A 2003 study of a Swedish family with epidermolytic palmoplantar keratoderma (EPPK) identified a de novo mutation in the keratin 9 gene (KRT9) on chromosome 17. The authors note that all previously reported EPPK mutations, with one exception, are in KRT9, and that the arginine codon at position 162 in exon 1 is the most frequently mutated site. A separate 2007 review states that EPPK, first described in 1901, may be the most common diffuse keratoderma and is characterised by keratosis restricted to palms and soles.
No randomised trial, no comparison against placebo or standard care, and no long-term follow-up data exist for any drug in EPPK. The genetic basis is well described, but what is missing is a properly funded clinical trial with clearly defined outcome measures, adequate sample size, and stratification by genotype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Dermatology · 1978 · 66 citations
AbstractThis study describes a family of 30 people in which 14 members have hereditary epidermolytic palmoplantar keratoderma. Four patients were treated with an oral aromatic retinoid for up to 5 months. They responded in a uniform and dramatic way: 10-14 days after the onset of therapy, the hyperkeratotic horny layer was sequestered in large sheets resulting in normal appearing skin and restoration of normal surface sensitivity. Biopsies revealed that the underlying disorder of keratinization had remained unchanged. Treatment with the retinoid had to be discontinued as the sensitivity and vulnerability restricted normal function of hands and feet. Epidermolytic hyperkeratosis (Frost & Van Scott, 1966) is a disorder of keratinization with distinctive histopathological (Ackermann, 1970; Frost & Van Scott, 1966; Lapière, 1932; Lapière, 1957) and ultrastructural (Anton-Lamprecht & Schnyder, 1974; Lapière, 1932; Lapière, 1957) characteristics which may be found in genetically transmitted diseases, certain types of naevi and hamartomas (Ackermann, 1970; Gebhart & Kidd, 1973; Plewig & Christophers, 1975; Schnyder, 1970) or, as an accidental feature, in a variety of acquired hyperkeratotic skin conditions (Ackermann, 1970; Plewig & Christophers, 1975). As a genodermatosis, epidermolytic hyperkeratosis in generalized expression presents as bullous ichthyosiform erythroderma (Frost & van Scott, 1966; Lapière, 1932; Lapière, 1957), but localized manifestations may assume the clinical appearance of hereditary linear naevus or hereditary palmoplantar keratoderma. In these localized lesions, the propensity to form bullae is minimal or absent. The epidermolytic variants of linear naevi and palmoplantar keratoderma thus do not differ appreciably from the common orthohyperkeratotic types, and the diagnosis is often made on an incidental basis. Although estimates of its incidence are a matter of speculation, epidermolytic hereditary palmoplantar keratoderma (EHPPK) appears to be exceedingly rare. Hitherto, only four affected families (Klaus, Weinstein & Frost, 1970; Voerner, 1901) and one single case (Brunsting et al., 1962) have
British Journal of Dermatology · 1985 · 14 citations
Epidermolytic variant of hereditary palmoplantar keratoderma
AbstractThe seventh family with autosomal dominant epidermolytic palmoplantar keratoderma is reported. The lesions are clinically indistinguishable from Unna-Thost disease but resemble epidermolytic hyperkeratosis (bullous ichthyosiform erythroderma) histopathologically. A skin biopsy is essential for making the correct diagnosis. One of our patients was treated with isotretinoin for 13 weeks without significant improvement.
British Journal of Dermatology · 2015 · 10 citations
Alitretinoin: treatment for refractory palmoplantar keratoderma
AbstractJournal Article Alitretinoin: treatment for refractory palmoplantar keratoderma Get access H.K. Park, H.K. Park Department of Dermatology Hanyang University College of Medicine Seoul 133‐792 South Korea Search for other works by this author on: Oxford Academic Google Scholar E.J. Kim, E.J. Kim Department of Dermatology Hanyang University College of Medicine Seoul 133‐792 South Korea Search for other works by this author on: Oxford Academic Google Scholar J.Y. Ko J.Y. Ko Department of Dermatology Hanyang University College of Medicine Seoul 133‐792 South Korea Correspondence: Joo Yeon Ko. E‐mail: [email protected] Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 5, 1 May 2016, Pages 1143–1144, https://doi.org/10.1111/bjd.14327 Published: 01 May 2016
AbstractA 38-year-old Japanese man was seen for severe palmoplantar keratoderma, extending to the dorsal aspects with red rims. He had had spontaneous amputations of the toes and surgical amputation of the right lower leg because of squamous cell carcinoma of the right sole. The clinical symptoms suggested those of mal de Meleda, except for the absence of consanguinity and of granular layers in the epidermis. The keratoderma improved with oral etretinate treatment.
A de Novo Mutation in the Keratin 9 Gene in a Family with Epidermolytic Palmoplantar Keratoderma from Northern Sweden
AbstractSir,Palmoplantar keratodermas (PPKs) constitute a hetero-geneous group of skin disorders with the distinctivetrait of hyperkeratosis of palmoplantar skin. Thedisorders are classified clinically by the morphologyand distribution of the hyperkeratosis, the presence ofassociated cutaneous and non-cutaneous features andby the mode of transmission (1, 2).Familial diffuse epidermolytic PPK (EPPK) is themost studied keratoderma and is characterized bygranular and vacuolar degeneration of the cells of thespinous and granular layer. All mutations reported todate, with one exception, are locatedinthekeratin9gene(KRT9)onchromosome17(1,3). The majority of KRT9mutations reported are missense mutations in exon 1of the KRT9 gene, but there are reports of a stopcodon mutation in exon 1 (4) and of a 3 base pairinsertion in exon 6 (5). The position most frequentlyreported to be mutated in KRT9 is the arginine codonat position 162 in exon 1. In addition to KRT9 mutations,there is a recent study revealing a splice site mutationin the KRT1 gene as the cause of mild EPPK (6).The KRT9 gene appears to be the only keratin genewhose expression is restricted to palmoplantar epider-mis (7, 8). Consequently, individuals that carry amutation in the keratin 9 gene only display the effect ofthe mutation in the palmoplantar skin.Here we report the first observation of a Swedishfamily with EPPK and the attribution of the disorder toa de novo mutation in KRT9.MATERIALS AND METHODS
AbstractEpidermolytic palmoplantar keratoderma (EPPK), first described by Vörner in 1901, may be the most common form of diffuse keratoderma and is characterized by keratosis restricted to the palms and soles. The disease is also known as keratosis palmaris et plantaris familiaris.KeywordsAutosomal Dominant DisorderEpidermolysis BullosaSecondary SyphilisEpidermodysplasia VerruciformisPalmoplantar KeratodermaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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.
