DeCure for Palmoplantar keratoderma, epidermolytic, 2
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for palmoplantar keratoderma, epidermolytic, 2 — 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 modulePalmoplantar keratoderma, epidermolytic, 2 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 palmoplantar keratoderma, epidermolytic, 2 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…
helix sheet bogdrag to rotate · scroll to zoom
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
Two patients with epidermolytic hereditary palmoplantar keratoderma were studied in 1988. Histology showed epidermolytic hyperkeratosis in the spinous and granular layers. Electron microscopy revealed aggregated tonofibrils, early keratohyaline granules, and vacuolar formation in epidermal cells, with some abnormalities present even in basal cells. Protein analysis found a decrease in 67-kilodalton keratin and the appearance of a 48-kilodalton keratin. Southern blot analysis of the 67-kilodalton keratin gene showed conserved gene organisation, leading the authors to suggest that regulatory abnormalities of keratinisation, rather than a structural gene defect, might be causative. In 2002, a Jewish family with five affected members was studied and a mutation was found in exon 1 of the keratin 9 gene at codon 160, consistent with most other families with this condition.
One case report from 1991 described a 38-year-old Japanese man with severe palmoplantar keratoderma extending to the dorsal aspects with red rims, who had spontaneous toe amputations and a surgical amputation of the right lower leg due to squamous cell carcinoma of the right sole. His keratoderma improved with oral etretinate treatment. A 2015 letter reported that alitretinoin was used for refractory palmoplantar keratoderma, but no patient numbers, response rates, or survival data are given in the abstract.
The 2013 review notes that palmoplantar keratodermas are a diverse group of hereditary and acquired disorders with diffuse, focal, or punctate patterns, and that clinical features such as extension beyond the palms and soles and associated systemic symptoms help distinguish each type. No controlled trials, no randomised data, and no quantitative treatment outcomes are available for epidermolytic palmoplantar keratoderma specifically. What is missing is a prospective trial with standardised outcome measures, any evidence that alitretinoin or etretinate works beyond single case reports, and a clear understanding of which patients might benefit from which drug.
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 · 1988 · 15 citations
Epidermolytic Hereditary Palmoplantar Keratoderma Histologic, Ultrastructural, Protein-Chemical, and DNA Analyses in Two Patients
Abstract• Two cases of epidermolytic hereditary palmoplantar keratoderma were studied by histologic, ultrastructural, protein-chemical, and genetic methods. Histologically, epidermolytic hyperkeratosis was seen at the spinous and granular layers. Electron microscopy showed the aggregation of tonofibrils and an early appearance of keratohyaline granules as well as vacuolar formation in the epidermal cells. Some of these morphologic abnormalities were detected even in the basal cells. The decrease of 67-kilodalton (kd) keratin and the appearance of 48-kd keratin were noted by using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Genetic analysis of the keratin gene family using 67-kd keratin complementary DNA by Southern blot analysis revealed the conserved gene organization of the 67-kd keratin gene. These findings suggest that undetermined regulatory abnormalities of keratinization, but not the gene structure itself, may be causative factors of this rare disease. (<i>Arch Dermatol</i>1988;124:555-559)
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.
Eponyms in the dermatology literature linked to Palmo-Plantar Keratoderma
AbstractPalmoplantar keratodermas (PPKs) represent a diverse group of hereditary and acquired disorders characterized by hyperkeratosis of the skin on the palms and soles The three major patterns of involvement are diffuse, focal and punctate. There are clinical distinguishing features for each disease in this group, for example, transmigration to areas beyond the palmoplantar skin. Also the extent of associated systemic symptoms if present help in characterization of each type.
Journal of the European Academy of Dermatology and Venereology · 2002 · 3 citations
Keratin‐9 gene mutation in a family with epidermolytic palmoplantar keratoderma
AbstractBACKGROUND: Epidermolytic palmoplantar keratoderma is an autosomal dominant inherited disorder of keratinization. METHODS: We studied five members of a Jewish family with epidermolytic palmoplantar keratoderma. Genomic DNA was extracted from leucocytes, and exon 1 of the keratin 9 gene was amplified using polymerase chain reaction techniques. RESULTS: The mutation was found in exon 1 of the keratin 9 gene in codon 160. CONCLUSIONS: Like most of the other families with clinical features of epidermolytic palmoplantar keratoderma the mutation is found in exon 1 of the keratin 9 gene.
Epidermolytic hereditary palmoplantar keratoderma. Histologic, ultrastructural, protein-chemical, and DNA analyses in two patients
Abstract• Two cases of epidermolytic hereditary palmoplantar keratoderma were studied by histologic, ultrastructural, protein-chemical, and genetic methods. Histologically, epidermolytic hyperkeratosis was seen at the spinous and granular layers. Electron microscopy showed the aggregation of tonofibrils and an early appearance of keratohyaline granules as well as vacuolar formation in the epidermal cells. Some of these morphologic abnormalities were detected even in the basal cells. The decrease of 67-kilodalton (kd) keratin and the appearance of 48-kd keratin were noted by using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Genetic analysis of the keratin gene family using 67-kd keratin complementary DNA by Southern blot analysis revealed the conserved gene organization of the 67-kd keratin gene. These findings suggest that undetermined regulatory abnormalities of keratinization, but not the gene structure itself, may be causative factors of this rare disease. (<i>Arch Dermatol</i>1988;124:555-559)
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.
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