DeCure for Non-epidermolytic palmoplantar keratoderma
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Non-epidermolytic palmoplantar keratoderma — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNon-epidermolytic palmoplantar keratoderma maps to a 4-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 non-epidermolytic palmoplantar keratoderma 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
Non-epidermolytic palmoplantar keratoderma is not directly studied in these abstracts. The 2019 and 2003 papers describe epidermolytic palmoplantar keratoderma (EPPK) caused by mutations in the keratin 9 (KRT9) gene. In a five-generation Chinese family with EPPK, a heterozygous c.T491C (p.L164P) mutation in KRT9 was found, and affected members showed diffuse palmoplantar keratosis, knuckle pads, friction-related lesions, and a novel symptom of palmar constriction. The 2003 paper reports a de novo mutation in KRT9 in a Swedish family with EPPK, noting that the arginine codon at position 162 in exon 1 is the most frequently mutated position in KRT9. Neither paper tests any drug treatment for the condition.
A 2021 systematic review of drug-induced palmoplantar keratoderma (PPK) included 247 patients (mean age 57.0 years; 60.3% male where sex was reported). PPK most frequently developed after BRAF inhibitors (73.7%, n=182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, n=38/247), tyrosine kinase inhibitors (3.2%, n=8/247), or chemotherapy (2.4%, n=6/247). The mean latency from drug start to PPK onset was 7.6 months (range 0.25–90 months). Improvement was reported in 24 cases: 50% achieved complete resolution and 50% partial resolution. All complete resolutions followed stopping the suspected drug, with a mean resolution period of 2.4 months (range 2 weeks–6 months). The most common treatments for PPK were keratolytic treatments (n=10) and topical corticosteroids (n=4). This review addresses acquired, drug-induced PPK, not hereditary non-epidermolytic forms.
A 2021 randomised controlled study of 70 patients with acquired plantar keratoderma compared iontophoresis combined with sodium salicylate (twice weekly for 8 weeks, 5–15 mA DC current for 10 minutes) to topical salicylic acid 12% ointment (twice daily for 8 weeks). Both groups showed statistically significant reduction in severity grading of parameters at 8 weeks, but intergroup values showed no significant difference. The mean Eczema Area Severity Index (EASI) score showed statistically significant reduction in the topical salicylic acid group compared to the iontophoresis group at week 8, and the percentage reduction in EASI score was also significantly higher with topical salicylic acid. The authors concluded that both treatments are safe and effective, with topical being slightly more efficacious, and that there is no additional benefit from drug delivery via iontophoresis. This study is limited to acquired plantar keratoderma and does not address hereditary non-epidermolytic palmoplantar keratoderma.
What is still missing: no clinical trial has tested any drug specifically for non-epidermolytic palmoplantar keratoderma. The genetic basis of the non-epidermolytic form is not covered by these abstracts. Funding for a dedicated trial, proper patient stratification by genotype, and a validated outcome measure for this orphan disease are all absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Molecular Genetics & Genomic Medicine · 2019 · 11 citations · open access
<i>Keratin 9</i> L164P mutation in a Chinese pedigree with epidermolytic palmoplantar keratoderma, cytokeratin analysis, and literature review
AbstractBACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is characterized by hyperkeratotic lesions on palms and soles. The disorder is caused by mutations of keratin 9 (KRT9) or KRT1 gene. METHODS: Epidermolytic palmoplantar keratoderma was diagnosed by physical examination and histopathological analysis in a five-generation Chinese family. Mutation was screened by Sanger sequencing. The palmar expression of multiple cytokeratins were analyzed by tape-stripping and Real-time PCR. Literatures of EPPK with additional symptoms were reviewed. RESULTS: Affected family members showed diffuse palmoplantar keratosis, with knuckle pads, friction-related lesions and a novel additional symptom of palmar constriction. A heterozygous mutation of c.T491C (p.L164P) of KRT9 was found within the helix initiation motif. The hydrophobic effect was decreased and the initiation of coiled-coil conformation was delayed. The KRT16/KRT6 expression were significantly increased in the patients, especially on the right, indicating activation of stress-response and wound-healing cytokeratins. There were also increased KRT9/KRT2, unchanged KRT10/KRT1, and undetectable KRT14/KRT5 expression. The genetic and phenotypic heterogeneity of EPPK with additional symptoms were summarized by literature review. CONCLUSION: The p.L164P mutation of KRT9 caused EPPK with a novel symptom of palmar constriction. The expression of multiple cytokeratins was altered in EPPK patients.
Journal of Cutaneous Medicine and Surgery · 2021 · 7 citations · open access
Drugs Associated With the Development of Palmoplantar Keratoderma: A Systematic Review
AbstractBackground Palmoplantar keratoderma (PPK) are a heterogenous group of hereditary and acquired disorders that are characterized by excessive epidermal thickening of the palms and/or soles. PPK has been described as a rare adverse event for some medications. The aim of this systematic review was to summarize outcomes in PPK associated with various medications. This data will assist dermatologists and other healthcare providers treating patients with drug-induced PPK. Methods EMBASE and MEDLINE databases were searched in accordance with PRISMA guidelines using the keyword “palmoplantar keratoderma.” 40 studies met the inclusion criteria. Results A total of 247 patients (mean age: 57.0 years) were included in the analysis. Among patients whose sex was reported, 60.3% ( n = 35/58) were male. PPK most frequently developed after treatment with BRAF inhibitors (73.7%, n = 182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, n = 38/247), tyrosine kinase inhibitors (TKIs) (3.2%, n = 8/247), or chemotherapy (2.4%, n = 6/247). The mean latency period between initiation of the drug and onset of PPK was 7.6 months (range: 0.25-90 months). Improvement of PPK was reported in 24 cases, with 50% ( n = 12/24) achieving complete resolution and 50% ( n = 12/24) achieving partial resolution. All patients who achieved complete resolution stopped the suspected drug, with a mean resolution period of 2.4 months (range: 2 weeks-6 months). The most common treatments for PPK were keratolytic treatments ( n = 10) and topical corticosteroids ( n = 4). Conclusions PPK was most frequently associated with targeted kinase inhibitors, specifically BRAF, MEK1/2, and tyrosine kinase inhibitors.
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
International Journal of Research in Dermatology · 2021 · 0 citations · open access
Efficacy and safety of iontophoresis combined sodium salicylate in acquired plantar keratoderma-a randomized controlled study
Abstract<p><strong>Background</strong>: Palmoplantar keratoderma is a heterogenous group of disorders, hereditary or acquired, characterized by thickening of palms and soles. Though it is not a life-threatening condition, it affects individual’s quality of life. As treatment of keratoderma has always been troublesome, upgraded treatment modalities which improves keratoderma efficiently are always encouraged.</p><p><strong>Methods</strong>: In this randomized controlled study, patients of plantar keratoderma of age group of 18-65 years were randomly divided in group A and group B. In group A, iontophoresis combined sodium salicylate was offered to patients twice weekly for 8 weeks of duration, during which DC current was supplied at 5-15 mA for 10 min of duration. Whereas, in group B patients applied topical salicylic acid 12% ointment at home twice a day for 8 weeks.</p><p><strong>Results</strong>: Our study of 70 patients of keratoderma, revealed diffuse (94%) pattern of involvement with female preponderance (55.7%) and occupation wise, most common among laborers (54.2%) followed by housewives (27.1%). Statistically significant number of patients showed reduction in severity grading of parameters, in both groups at end of 8 weeks. Same way, mean values of parameter grading significantly reduced at 8 weeks in both the groups. But intergroup values showed no significant difference. Mean EASI (Eczema Area Severity Index) score showed statistically significant reduction in group B as compared to group A at 8<sup>th</sup> week. Percentage of reduction of EASI score was also significantly higher in group B at end of treatment.</p><p><strong>Conclusions:</strong> Here both treatment modalities are safe and effective, topical being slightly more efficacious than iontophoresis. So, we can conclude that no additional privilege of drug delivery through iontophoresis.</p>
Sage Journals Data · 2021 · 0 citations · open access
Drugs Associated With the Development of Palmoplantar Keratoderma: A Systematic Review
AbstractBackgroundPalmoplantar keratoderma (PPK) are a heterogenous group of hereditary and acquired disorders that are characterized by excessive epidermal thickening of the palms and/or soles. PPK has been described as a rare adverse event for some medications. The aim of this systematic review was to summarize outcomes in PPK associated with various medications. This data will assist dermatologists and other healthcare providers treating patients with drug-induced PPK.MethodsEMBASE and MEDLINE databases were searched in accordance with PRISMA guidelines using the keyword “palmoplantar keratoderma.” 40 studies met the inclusion criteria.ResultsA total of 247 patients (mean age: 57.0 years) were included in the analysis. Among patients whose sex was reported, 60.3% (<i>n</i> = 35/58) were male. PPK most frequently developed after treatment with BRAF inhibitors (73.7%, <i>n</i> = 182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, <i>n</i> = 38/247), tyrosine kinase inhibitors (TKIs) (3.2%, <i>n</i> = 8/247), or chemotherapy (2.4%, <i>n</i> = 6/247). The mean latency period between initiation of the drug and onset of PPK was 7.6 months (range: 0.25-90 months). Improvement of PPK was reported in 24 cases, with 50% (<i>n</i> = 12/24) achieving complete resolution and 50% (<i>n</i> = 12/24) achieving partial resolution. All patients who achieved complete resolution stopped the suspected drug, with a mean resolution period of 2.4 months (range: 2 weeks-6 months). The most common treatments for PPK were keratolytic treatments (<i>n</i> = 10) and topical corticosteroids (<i>n</i> = 4).ConclusionsPPK was most frequently associated with targeted kinase inhibitors, specifically BRAF, MEK1/2, and tyrosine kinase inhibitors.
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.
