DeCure for Palmoplantar keratoderma, Nagashima type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for palmoplantar keratoderma, Nagashima type — 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, Nagashima type 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, nagashima type 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.
What the evidence adds up to
A 2010 review notes that Nagashima-type palmoplantar keratoderma was first described in Japan in 1977, and by 2010 about 20 cases had been reported in the Japanese literature. A 2024 case report describes a female patient of Korean descent with a heterozygous SERPINB7 mutation who had adult-onset Nagashima-type palmoplantar keratoderma and then achieved spontaneous clinical remission. The authors state this is the first reported heterozygous SERPINB7 mutation carrier with classic NPPK to have such a remission.
A 2018 study of a large Chinese pedigree with diffuse nonepidermolytic palmoplantar keratoderma (NEPPK) identified a novel splice-site mutation c.1255-1G>C in intron 6 of KRT1 in all 11 affected individuals. The authors note that diffuse NEPPK is a relatively rare subtype of palmoplantar keratoderma and that the finding expands the spectrum of KRT1 mutations. That study did not involve Nagashima-type specifically, but the broader category of diffuse NEPPK.
A 2024 surgical case report describes a five-year-old girl with severe palmoplantar keratoderma resistant to medical management, who was wheelchair-bound and had repeated hospital admissions for sepsis. After excision of keratoderma down to subcutaneous tissue on feet and hands, with Integra and split-thickness skin grafts, and later a rectus free flap for a heel breakdown, the patient after 16 years was a college student who could walk, take notes, type, and had almost full finger range of motion. The authors state this surgical approach has not been reported before with 16-year follow-up data, but they do not specify the genetic subtype of palmoplantar keratoderma.
What is still missing is a clear genetic diagnosis in the surgical case, larger case series or trials for any intervention in Nagashima-type specifically, and any drug treatment tested in a controlled manner for this condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Dermatology · 2010 · 5 citations
A familial case of Nagashima-type palmoplantar keratosis
AbstractAuteur(s) : Satoshi Nakamizo, Kenzo Takahashi, Yoshiki Miyachi, Kenji Kabashima Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara, Sakyo, Kyoto, 606-8507, Japan “Nagashima-type” keratosis palmoplantaris is characterized by transgressive and non-progressive palmoplantar keratosis (PPK), which was first described in a 1977 report from Japan [1]. Since then, about 20 cases have been reported in the Japanese literature [2] until recently, [...]
Underline Science Inc. · 2024 · 0 citations · open access
Cutting Through Complexity: Surgical Management of a Severe Palmoplantar Keratoderma
AbstractBackground Palmoplantar keratoderma is a rare condition characterized by progressive thickening of the skin on the palms and soles of the feet. In severe cases, it can lead to complications such as sepsis and lifelong disabilities. Traditionally, it has been managed medically with emollients, keratolytics, vitamin supplementation, and surgically with debridement, often leading to recurrence. We present this clinical vignette to highlight the management of severe palmoplantar keratoderma through a nuanced approach involving tissue excision down to the subcutaneous level. To our knowledge, based on a PubMed search using 'Keratoderma, Palmoplantar, Diffuse' [Mesh] and reviewing 265 articles, this approach has not been reported before with 16-year follow-up data. Methods The patient presented as a five-year-old girl with severe palmoplantar keratoderma, resistant to medical management. She had been wheelchair-bound with repeated hospital admissions for sepsis. She was initially managed with episodic deep debridement, which offered temporary relief followed by rapid recurrence. After obtaining informed consent, the decision was made to excise the keratoderma from her feet, removing the dermis and subcutaneous tissue. After excision, Integra was placed with negative pressure wound therapy (NPWT), followed by a second layer of Integra with NPWT. Final coverage was achieved with a thin split-thickness graft. For the hands, a similar procedure was performed with excision down to the palmar fascia, extending to the subcutaneous tissue of the fingers, which were pinned straight to reduce the possibility of contracture. After negative pressure wound therapy and granulation, a thin split-thickness skin graft was placed. After 6 months of walking as a middle school student, there was a breakdown of the heel to the plantar fascia, which was managed using a rectus free flap for heel reconstruction, followed by a conventional split-thickness skin graft. The flap subsequently shrank, with no recurrence. Results After 16 years, the patient is now a college student who walks with stability in her hands and feet. She can take notes, type, and has almost a full range of motion in her fingers. The patient reports that she is able to lead a normal and productive life. Conclusion Our case report highlights a novel surgical approach that can potentially be used for the treatment of severe palmoplantar keratoderma. It also underscores the challenges of managing this rare and severe condition with conventional treatments and emphasizes the need for innovative surgical solutions for its management.
Genetic Testing and Molecular Biomarkers · 2018 · 0 citations
Novel Splice-Site Mutation of <i>KRT1</i> Underlies Diffuse Palmoplantar Keratoderma in a Large Chinese Pedigree
AbstractAIMS: To identify potential causative gene mutations in a large Han Chinese pedigree with diffuse nonepidermolytic palmoplantar keratoderma (NEPPK). METHODS: We enrolled 11 patients and 8 healthy individuals from a pedigree with NEPPK and 100 randomly selected healthy controls. Biopsy samples were obtained from the proband. Genomic DNA was extracted from a peripheral blood sample from each participant. Mutation detection via polymerase chain reaction and Sanger sequencing of relevant potential causative genes, including KRT1, KRT6C, KRT10, KRT16, AQP5, and SERPINB7, was performed. Comparisons were made between sequencing outcomes and currently available reference genome databases, including HGMD Pro, Pubmed, 1000 Genomics, and dbSNP. RESULTS: Histological findings, clinical features, and medical history were in accordance with the diagnosis of diffuse NEPPK. We identified a novel splice-site mutation c.1255-1G > C in intron 6 of KRT1 in all individuals with NEPPK in the pedigree. CONCLUSIONS: Diffuse NEPPK is a relatively rare subtype of palmoplantar keratoderma. The results of this study expand the spectrum of KRT1 mutations in diffuse NEPPK and provide insights into the understanding of its underlying pathological mechanisms and phenotype-genotype correlations.
Spontaneous clinical remission of Nagashima‐type palmoplantar keratoderma in a patient of Korean descent with a heterozygous SERPINB7 mutation
AbstractNagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive form of diffuse palmoplantar keratoderma (PPK) characterized by thickening and redness of palms and/or soles. In this report, we describe a female patient of Korean descent who had clinical remission of her adult-onset NPPK. To our knowledge, she is the first reported heterozygous SERBINB7 mutation carrier to present with classic NPPK who achieved spontaneous clinical remission.
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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