DeCure for Autosomal dominant palmoplantar keratoderma and congenital alopecia
DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for autosomal dominant palmoplantar keratoderma and congenital alopecia — 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 moduleAutosomal dominant palmoplantar keratoderma and congenital alopecia 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 autosomal dominant palmoplantar keratoderma and congenital alopecia 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
gap junction protein alpha 1 (GJA1) — GJA1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7Z1T · 2.26 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 1985 Swedish survey of hereditary palmoplantar keratoderma in Norrbotten county, two clinical forms were distinguished: a common autosomal dominant type (Unna-Thost variety) and a severe autosomal recessive type. One recessive patient had mutilating palmoplantar keratoderma. Neither employment nor dermatophytosis influenced the severity of hyperkeratosis in either type.
A 2010 case report described a 10-year-old girl with generalised atrichia and severe palmoplantar keratoderma causing pseudo-ainhum, sclerodactyly, and contractures. Sequencing of GJB2 and LOR coding regions was normal. Reviewing the literature, the authors proposed two distinct types of palmoplantar keratoderma with congenital alopecia: an autosomal dominant form (Stevanović type) that is variable and benign without significant hand complications, and an autosomal recessive variant (Wallis type) with contractures, sclerodactyly, and pseudo-ainhum. Nuclear cataract may be an additional but not constant finding in the Wallis type.
A 1990 report described two sons of consanguineous, phenotypically normal Arab parents who presented with patchy eczematous lesions followed by palmoplantar keratoderma and raised serum IgE. Skin biopsy showed epidermolytic hyperkeratosis. The authors suggested autosomal recessive inheritance, but no gene mutation was identified.
A 2002 study of five members of a Jewish family with epidermolytic palmoplantar keratoderma found a mutation in exon 1 of the keratin 9 gene at codon 160, consistent with most other families with this autosomal dominant disorder. No treatment or drug intervention was tested in any of these studies. What remains missing are prospective trials of any therapy, systematic genetic characterisation of the recessive forms, and patient stratification by molecular diagnosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 1985 · 40 citations
Two different clinical and genetic forms of hereditary palmoplantar keratoderma in the northernmost county of Sweden
AbstractA follow-up study of clinical and genetic observations, made on patients with hereditary palmoplantar keratoderma living in the northernmost county of Sweden (Norrbotten) in 1967, was performed. Two clinical types could be distinguished, a common form with an autosomal dominant mode of inheritance, corresponding to the description of the Unna Thost variety and a severe form with evidently an autosomal recessive inheritance. One of the patients with the severe form had a mutilating palmoplantar keratoderma. Neither employment nor dermatophytosis influenced the severity of the hyperkeratosis in any of these two types. Occurrence of hereditary palmoplantar keratoderma together with other genodermatoses of dermatoses with a polygenic mode of inheritance was also found in this study.
American Journal of Medical Genetics Part A · 2010 · 19 citations
Palmoplantar keratoderma, pseudo‐ainhum, and universal atrichia: A new patient and review of the palmoplantar keratoderma‐congenital alopecia syndrome
AbstractPalmoplantar keratoderma (PPK) may concur with congenital alopecia (CA) in various genodermatoses. We report on a 10-year-old girl with generalized atrichia and a severe form of PPK causing pseudo-ainhum, sclerodactyly, and contractures, a phenotype not consistent with any well-defined condition. Non-specific additional findings comprised mild nail dystrophy and widespread keratosis pilaris including ulerythema ophryogenes. Direct sequencing of the GJB2 and LOR coding regions yielded normal results. A review identified two additional sporadic and four familial cases with PPK and CA. Comparison between familial cases suggested the existence of two genetically and phenotypically distinct types of PPK-CA: (i) an autosomal dominant form (Stevanović type), a variable and benign phenotype without significant hand complications, and (ii) a more complex autosomal recessive variant (Wallis type) with contractures, sclerodactyly, and pseudo-ainhum. Nuclear cataract may represent an additional although not constant finding in the Wallis type PPK-CA. Further reports are required to test this preliminary conclusion.
AbstractPalmoplantar keratoderma (PPK) is a heterogeneous group of disorders. Epidermolytic PPK is a well delineated autosomal dominant entity, but no recessive form is known. Here we report two sons of phenotypically normal, consanguineous, Arab parents with features suggestive of PPK. They presented with patchy eczematous skin lesions followed by PPK and raised serum levels of IgE. Skin biopsy from the keratotic lesions showed the features of epidermolytic hyperkeratosis. Autosomal recessive inheritance is suggested and the differential diagnosis is discussed.
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.
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.
