DeCure for Autosomal recessive palmoplantar keratoderma and congenital alopecia
DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for autosomal recessive 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 recessive 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 recessive 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
lanosterol synthase (LSS) — LSS 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 1W6K · 2.1 Å · ligand octyl beta-D-glucopyranoside (BOG). Experimental structure, not a prediction.
What the evidence adds up to
A brother and sister with Meleda keratoderma, an autosomal recessive palmoplantar keratoderma with transgrediens and progrediens features, ainhum-like narrowings and lesions at other sites, were treated with the aromatic retinoid etretinate. Clinical and histological results after nine months of treatment were reported in 2009, but the abstract gives no numerical outcomes such as clearance rates or survival data. No control group is described.
Three siblings with Olmsted syndrome, a congenital transgredient palmoplantar keratoderma with periorificial hyperkeratotic plaques, flexion deformities, localised alopecia, leukokeratosis of the tongue, short stature and large joint laxity, were treated with topical corticosteroids and emollients. The 2017 report states only mild improvement in symptoms. The disease course is described as slow, progressive and extremely disabling. No quantitative measures of improvement are provided.
A 2020 study used whole exome sequencing in one affected individual and her healthy mother to identify loss-of-function variants in SERPINA12 as the cause of an autosomal recessive palmoplantar keratoderma. The data set consists of the sequencing analysis results. No treatment was tested, and no clinical outcomes are reported.
What is still missing: larger, genetically confirmed patient cohorts; any controlled trial of retinoids, topical corticosteroids or other agents; quantitative outcome measures such as symptom scores or time to progression; and stratification by the specific genetic subtype, which may determine whether a given treatment has any effect.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Dermatologica · 2009 · 31 citations
Unusual Cases of Meleda Keratoderma Treated with Aromatic Retinoid Etretinate
AbstractWe studied a brother and sister of South Italian origin with palmoplantar keratoderma which, because of the clinical aspects (transgrediens et progrediens), mode of inheritance (autosomal recessive) and evolution, we diagnosed as Meleda keratoderma with particular clinical features (presence of ainhum-like narrowings and concomitant lesions at other sites). Appropriate classical histologic and familial investigations, as well as HLA typing were done, and retinol-binding protein values were determined. The patients were treated with the aromatic retinoid etretinate, and the clinical and histological results after 9 months' treatment are reported.
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.
Indian Journal of Paediatric Dermatology · 2017 · 0 citations · open access
Olmsted syndrome in three siblings
AbstractOlmsted syndrome (OS) is a rare congenital, sharply circumscribed transgredient palmoplantar keratoderma, first described by Olmsted in 1927, characterized by clinical features such as symmetrical involvement of keratoderma of the palms and soles and the symmetrical hyperkeratotic plaques around the body orifices. Other clinical findings include flexion deformities of the fingers, localized alopecia, leukokeratosis of the tongue, short stature, and laxity of the large joints. It starts in the neonatal period or in childhood. The disease has a slow but progressive and extremely disabling course. Treatment of OS is often based on topical therapy with retinoic acid, corticosteroid, emollients, and keratolytics. We present a case of OS in three siblings, two males and a female, born to nonconsanguineous parents with no family history. They were treated with topical corticosteroids and emollients and showed mild improvement in symptoms.
Data Archiving and Networked Services (DANS) · 2020 · 0 citations · open access
Loss-of-function variants in SERPINA12 underlie autosomal recessive palmoplantar keratoderma
AbstractInherited palmoplantar keratodermas (PPKs) refer to a large and heterogeneous group of conditions resulting from abnormal epidermal differentiation and featuring thickening of the skin of the palms and soles. Here, we aimed at delineating the genetic basis of an autosomal recessive form of PPK. We conducted whole exome sequencing (WES) in affected individual and healthy mother. This data set includes the WES analysis results.
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.
