DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for inherited isolated nail anomaly — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInherited isolated nail anomaly maps to a 2-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 inherited isolated nail anomaly 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
frizzled class receptor 6 (FZD6) — FZD6 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 8JHB · 3.3 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2021 report describes an 18-year-old patient with hereditary distal onycholysis (HDO) affecting all nails since birth, with smooth, thick nails and a concave proximal edge of detachment. The patient had difficulty cutting the nails and marked sensitivity to cold, especially after cold water exposure, but no skin colour changes, ruling out Raynaud phenomenon. Several relatives showed similar abnormalities, with an autosomal dominant inheritance pattern. The report notes that no effective therapy has been reported and that nail dystrophy may persist with no or little improvement. A 2017 review states that mutations in five genes have been identified as a cause of isolated hereditary nail disorders, but the precise roles of these genes in nail development and regeneration have not been completely disclosed.
A 2024 review of paediatric nail disorders notes that non-syndromic congenital nail disorders include anonychia/hyponychia, congenital malalignment of the great toenail, and racket thumbs, each with distinct clinical presentations and genetic associations. The review emphasises that congenital nail disorders encompass both isolated anomalies and syndromic associations, requiring thorough evaluation for associated systemic conditions. It also states that acquired nail diseases in children, such as Beau's lines and onychomadesis, typically result from trauma or infection.
The 2021 report explicitly states that diagnosis of HDO is clinical, based on decreased growth rate, thick nails, and a straight or concave proximal edge of detachment since childhood, with a positive family history. Cold sensitivity and palmoplantar hyperhidrosis are key associated features. The report lists several hereditary disorders that can resemble HDO, including hidrotic ectodermal dysplasia and pachyonychia congenita, and notes that the main challenge is to differentiate HDO from other isolated hereditary nail disorders. No effective therapy has been reported for HDO.
What is still missing is any clinical trial data for treatments in isolated hereditary nail disorders, including HDO. The genetic pathways are partially understood but not fully disclosed, and no targeted therapies have been developed. Patient stratification by specific gene mutation is not yet possible in clinical practice, and funding for research into these rare conditions remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractBackground: Pediatric nail disorders encompass a broad range of conditions. This article aimed to consolidate current knowledge on pediatric nail disorders to enhance diagnostic proficiency and clinical management among healthcare professionals. Summary: Pediatric nail disorders present a diagnostic challenge due to their diverse nature. Non-syndromic congenital nail disorders encompass various anomalies such as anonychia/hyponychia, congenital malalignment of the great toenail, and racket thumbs, each with distinct clinical presentations and genetic associations. Syndromic congenital nail disorders, often part of complex syndromes, are characterized by unique features and associated abnormalities. Acquired nail diseases in children, like Beau's lines and onychomadesis, typically result from trauma or infection, while melanonychia, although rare in children, requires careful monitoring for potential malignant alterations, with consideration for biopsy in cases with concerning features. Key Messages: (1) Pediatric nail disorders may pose diagnostic challenges and require a comprehensive understanding of nail anatomy and development. (2) Congenital nail disorders encompass isolated anomalies and syndromic associations, necessitating thorough evaluation for associated systemic conditions. (3) Acquired nail diseases may indicate underlying trauma or systemic illness and require careful assessment.(4) Melanonychia in children requires ongoing monitoring and evaluation, emphasizing the importance of consistent follow-up and histopathological examination when necessary.
Indian Journal of Dermatology · 2021 · 0 citations · open access
Hereditary Distal Onycholysis
AbstractInherited nail disorders are a rare and heterogeneous group of diseases. Hereditary distal onycholysis (HDO) is classified into the group of isolated hereditary nail disorders and is characterized by a slow growth of nails, thick and hard nails, and a straight or concave proximal edge of detachment.[1] We report an 18-year-old patient who has suffered from onycholysis of all the nails since birth. He has no relevant medical history. Clinical examination revealed nails were smooth, thick, and showed a concave proximal edge of detachment [Figure 1]. Apart from cosmetic disability, our patient complained about the difficulty to cut them and a marked sensibility to cold, particularly on the hands and feet and especially after exposure to cold water. No skin changes were noticed so Raynaud's phenomenon was discarded. The patient did not complain of hyperhidrosis. Examination of skin, teeth, hair, and mucosae proved no abnormalities. Blood analysis and X-rays of hands and feet were normal. Nails evaluation with direct microscopy as well as mycological cultures were negative. Several relatives showed similar abnormalities [Figure 2]. The inheritance appeared to be autosomal dominant [Figure 3].Figure 1: Nails of the 18-year-old index patient. Onycholysis with a concave proximal edge of detachment, scleronychia and absent lunulae in all the nailsFigure 2: Nails of the patient's mother. Onycholysis with a concave proximal edge of detachment, scleronychia and absent lunulae in all the nailsFigure 3: Family history. The 18-year-old index patient is marked by an arrowThe features of the family we describe are comparable to the families reported with HDO. Shulze (1966) described a family where several members showed onycholysis since childhood.[2] It was associated with a slow nail growth, scleronychia, and absent lunulae. Hypersensitivity to cold and palmoplantar hyperhidrosis were frequently linked symptoms. No changes in the skin, teeth, hair, or mucosae were seen. Subsequently, Burg (1975) reported a family with similar characteristics.[3] Affected individuals did not present palmoplantar hyperhidrosis or sensitivity to cold, but itchy fingers. Finally, Bazex et al.[4] described a new family with onycholysis of all nails in several members, decreased nail growth, and scleronychia. In addition, all affected members except one showed palmoplantar hyperhidrosis and sensitivity to cold. There are various hereditary disorders that could resemble the nails of the family we describe.[5] Hidrotic ectodermal dysplasia is an autosomal dominant disorder characterized by nails that gradually become thickened, often with onycholysis, together with hypotrichosis and palmoplantar keratoderma. Pachyonychia congenita is an autosomal dominant inherited disease associated with nail thickening, more marked in toenails, and painful plantar keratoderma. The main challenge is to differentiate HDO from other isolated hereditary nail disorders. A decreased growth rate, thick nails, and a straight or concave proximal edge of detachment since childhood, in patients with a positive familiar history highly suggest the diagnosis. In addition, cold sensitivity and palmoplantar hyperhidrosis are key features that may be associated. Excessive sensitivity to cold expresses an exaggerated response with pain and tenderness when affected patients are exposed to a cold environment. In contrast to Raynaud phenomenon, affected patients do not manifest skin color changes. Diagnosis of HDO is clinical. An appropriate anamnesis including past medications and family history in combination with physical examination with emphasis to ectodermal structures are helpful in diagnosing HDO. None effective therapy has been reported and nail distrophy may persist with no or little improvement. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Encyclopedia of Life Sciences · 2017 · 0 citations
Genetics of Isolated Hereditary Nail Disorder
AbstractAbstract Recent advances in molecular genetics and emergence of next‐generation genomic tools have led to the identification of many genes expressed in nail matrix/bed. However, the precise roles of these genes in the nail development and regeneration have not completely been disclosed. Using the methods of forward genetics, a series of genes responsible for hereditary nail disorders have recently been identified. Furthermore, expression and functional analyses have gradually revealed that these genes are directly or indirectly related with each other. This article briefly discusses the clinical and genetic perspective on defining and classifying isolated hereditary nail disorders and the overlapping genetic pathways. The journey towards unravelling the molecular basis of hereditary nail disorders will contribute to better understanding of the complex mechanisms for nail morphogenesis and development in humans. Key Concepts Genetic and non‐genetic factors contribute to nail diseases. Hereditary nail disorders may exist as an isolated entity or associated with other diseases. Underlying genes in nail disorders and signalling pathways in nail development can provide a logical basis for the classification of genetic disorders of nail. To date, mutations in five genes have been identified as a cause of isolated hereditary nail disorders. Development of nail unit requires epithelial–mesenchymal interactions. Wnt signalling pathway is crucial for maintaining epithelial–mesenchymal interaction. Lipid biosynthesis is required for the development and maintenance of proper nail structure.
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.
