DeCure for Palmoplantar keratoderma, nonepidermolytic, focal 1
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for palmoplantar keratoderma, nonepidermolytic, focal 1 — 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, nonepidermolytic, focal 1 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, nonepidermolytic, focal 1 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
The abstracts describe palmoplantar keratoderma as a heterogeneous group of inherited and acquired disorders characterised by persistent epidermal thickening of the palms and soles. The three major patterns are diffuse, focal/striate, and papular/punctate. Some forms affect only the skin; others have syndromic features including changes in hair, teeth, nails, hearing loss, or cardiomyopathy. Next generation sequencing has helped discover genes involved in many of these conditions and led to reclassification. No drug treatment is mentioned in any of the abstracts.
One abstract reports a mutation in exon 1 of the keratin 9 gene, in codon 160, in a Jewish family with epidermolytic palmoplantar keratoderma. This is a genetic finding, not a therapeutic result. No drug was tested or proposed.
A 2024 case report describes a single patient with severe palmoplantar keratoderma resistant to medical management. The patient was a five-year-old girl, wheelchair-bound with repeated hospital admissions for sepsis. She was managed surgically, not with drugs: excision of keratoderma from the feet down to subcutaneous tissue, Integra placement with negative pressure wound therapy, and thin split-thickness skin graft. For the hands, excision down to the palmar fascia with finger pinning, followed by negative pressure wound therapy and skin graft. After 16 years, the patient is a college student who walks with stability, can take notes and type, and has almost full range of motion in her fingers. The authors note this surgical approach has not been reported before with 16-year follow-up data. No drug was used.
What is still missing: no drug has been tested in a controlled trial for this condition. The only intervention with long-term outcome data is a single surgical case report. There is no evidence for any pharmacological treatment, no patient stratification by genetic subtype, and no funding for a drug trial in nonepidermolytic focal palmoplantar keratoderma.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diagnosis and Management of Inherited Palmoplantar Keratodermas
AbstractInherited monogenic palmoplantar keratodermas are a heterogeneous group of conditions characterised by persistent epidermal thickening of the palmoplantar skin. Palmoplantar keratodermas are grouped depending on the morphology of the keratoderma into diffuse, focal/striate or papular/punctate. Some palmoplantar keratodermas just affect the skin of the palms and soles and others have associated syndromic features which include changes in hair, teeth, nails, hearing loss or cardiomyopathy. Next generation sequencing has helped discover genes involved in many of these conditions and has led to reclassification of some palmoplantar keratodermas. In this review, we discuss the diagnostic features of palmoplantar keratodermas and management options.
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.
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.
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.
