DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for tooth and nail syndrome — 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 moduleTooth and nail syndrome 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 tooth and nail syndrome 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 2011 study identified a homozygous nonsense mutation in the FZD6 gene (c.1750G>T, p.E584X) in two Pakistani families with autosomal-recessive nail dysplasia. The mutation was mapped to chromosome 8q22.3. Immunohistochemistry in healthy nail sections showed strong FZD6 expression in the ventral nail matrix and weaker expression in the nail bed. FZD6 encodes the Wnt receptor frizzled 6, which acts as a negative regulator of canonical Wnt signalling and a positive regulator of noncanonical Wnt pathways. The authors concluded that FZD6 plays a role in nail plate growth and guidance. Only seven FZD6 mutations had been reported by 2019.
The 2019 study reported a homozygous 8 bp deletion in FZD6 (c.1676_1683delGAACCAGC, p.Gly559Aspfs*16) in a consanguineous Turkish family with nail dysplasia. This frameshift creates a premature stop codon. Molecular dynamics simulations predicted that the mutation changes the protein’s entropy in a negative manner, disrupting the C-terminal domain structure and its interaction partners. The study provided a proposed pathogenicity mechanism for this specific deletion but did not test any treatment.
A 2004 review of nail disorder treatment noted that nail plate growth is slow (3 mm/month in fingernails, 1–1.5 mm/month in toenails), so treatment results take months to appear. Topical drug delivery through the nail is difficult because vehicles effective for skin penetration do not work on the nail. Most topical drugs are ineffective for inflammatory nail disorders. Clinicians often avoid systemic treatment when disease is limited to the nails. A 1989 paper on nail biting (onychophagia) reported it affects 20–30% of the population and can cause psychosocial problems and complications in the nail unit and oral cavity, but this is a separate condition from the genetic nail dysplasia described in the other abstracts.
No clinical trial has tested any drug for FZD6-related nail dysplasia. No treatment, topical or systemic, has been evaluated in patients with this specific genetic mutation. What is missing is any funded clinical study, a trial design that accounts for the slow nail growth and poor topical drug penetration noted in the 2004 review, and patient stratification by specific FZD6 mutation type.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Dermatology · 2011 · 46 citations
<i>FZD6</i>encoding the Wnt receptor frizzled 6 is mutated in autosomal‐recessive nail dysplasia
AbstractBACKGROUND: Isolated nail dysplasia is rare and has been reported in only a small number of families. OBJECTIVES: To describe and characterize two Pakistani families with an autosomal-recessive inherited nail dysplasia. METHODS: Genome-wide linkage analysis; mutation screening of candidate genes by Sanger sequencing; cloning of FZD6 and protein analyses; immunohistochemistry. RESULTS: We mapped this genodermatosis to chromosome 8q22.3, and identified a homozygous nonsense mutation c.1750G>T (p.E584X) in the frizzled 6 (FZD6) gene in all affected individuals. Immunohistochemical analyses in nail sections from healthy individuals revealed strong expression of FZD6 in the ventral nail matrix and a less pronounced expression of FZD6 in the nail bed. CONCLUSIONS: FZD6 belongs to a family of proteins that serve as receptors in Wnt signalling pathways, and has been shown to act as a negative regulator of the canonical Wnt/β-catenin signalling cascade and a positive regulator of the noncanonical Wnt or planar cell polarity pathway. The present results therefore suggest that FZD6 plays a pivotal role in the growth and guidance of the nail plate in humans by acting as a molecular switch between different Wnt pathways. Previous studies have identified mutations in the RSPO4 and LMX1B components of the Wnt pathway in patients with the hypoplastic nail disorders anonychia and nail-patella syndrome, respectively. Only recently, FZD6 mutations were identified in isolated nail dysplasia. The present results emphasize the important role of the Wnt pathways in nail development and increase understanding of Wnt-mediated developmental events in general.
Yellow nail syndrome associated with penicillamine therapy
AbstractA patient is described in whom the nail changes of the yellow nail syndrome developed whilst she was taking penicillamine. Stopping the drug was associated with resolution of the nail changes. The yellow nail syndrome was first described in 1964 (Samman and White), but the cause is still unknown. Impaired lymphatic drainage is thought to be a factor in the pathogenesis, and lymphoedema is often an accompanying feature. We describe a case in which nail changes, typical of those described in the yellow nail syndrome, occurred in a patient treated with d-penicillamine, and in whom the nails reverted to normal on withdrawing the drug. (Received March 15, 1983.)
Case Reports in Dentistry · 2016 · 16 citations · open access
New Approach to Managing Onychophagia
AbstractOnychophagia is defined as a chronic habit of biting nails, commonly observed in both children and young adults. This oral habit may lead to various medical and dental problems. To date, onychophagia is considered an unsolved problem in medicine and dentistry. In this paper we describe an exclusive nonpunitive fixed appliance utilizing a stainless steel twisted round wire bonded from canine to canine, in the mandibular arch, as a treatment of onychophagia. It was used successfully in young adult patients and maintained for a month. With 9-month follow-up the treatment has satisfied the patients' expectations which may eventually yield promising implications of this new treatment to similar situations.
BMC Medical Genetics · 2019 · 11 citations · open access
A possible founder mutation in FZD6 gene in a Turkish family with autosomal recessive nail dysplasia
AbstractBACKGROUND: Autosomal recessive nail dysplasia is characterized by thick and hard nails with a very slow growth on the hands and feet. Mutations in FZD6 gene were found to be associated with autosomal recessive nail dysplasia in 2011. Presently, only seven mutations have been reported in FZD6 gene; five mutations are clustered in the C-terminus, one is at the seventh transmembrane domain, and another is at the very beginning of third extracellular loop. METHODS: Whole exome sequencing (WES) was applied to the index case, her one affected sister and her healthy consanguineous parents. The mutation was verified via Sanger sequencing. Molecular dynamics simulations of the predicted structures of native and mutant proteins were compared to gain insight into the pathogenicity mechanism of the mutation. RESULTS: Here, we report a homozygous 8 bp deletion mutation, p.Gly559Aspfs*16; c.1676_1683delGAACCAGC, in FZD6 gene which causes a frameshift and creates a premature stop codon at position 16 of the new reading frame. Our molecular dynamics calculations predict that the pathogenicity of this frameshift mutation may be caused by the change in entropy of the protein with negative manner, disturbing the C-terminal domain structure, and hence interaction partners of FZD6. CONCLUSION: We identified a homozygous deletion mutation in FZD6 in a consanguineous Turkish family with nail dysplasia. We also provide a molecular mechanism about the effects of the deletion on the protein structure and its possible motions. This study provides a pathogenicity mechanism for this mutation in nail dysplasia for the first time.
AbstractThere are several reasons that make the nail unit difficult to treat. It is necessary to wait for several months before seeing the results of treatments in nail disorders, as the nail plate grows very slowly (average nail growth is 3 mm/month in fingernails and 1-1.5 mm/month in toenails). It is very important to give the patients this information, as they may otherwise discontinue the treatment feeling it to be ineffective. Delivery of topical drugs through the nail is difficult, as vehicles utilized for enhancing penetration of drugs through the skin are not effective in the nail. Most topical drugs are therefore ineffective in the treatment of inflammatory nail disorders, since the nails are largely exposed to environmental hazards and nail disorders are commonly precipitated or worsened by physical traumas. Thus, clinicians often do not prescribe systemic treatment when the disease is limited only to the nails
Cambridge University Press eBooks · 2010 · 2 citations
Intimate Partner Violence: Aggression at Close Quarters
AbstractThis chapter uses the phrase nail biting rather than onychophagia because nail biting is more easily understood. Although most nail biters bite only their fingernails, some people bite their toenails as well or overclip their toenails. Occasionally, people may bite their nails as part of a behavioral disorder occasioned by intense pain. Nail biting can be reliably and simply measured by using calipers. For older teenagers and adults, the data from Malone and Massler's study indicate that fewer girls and women than boys and men bite their nails. Studies of obsessive-compulsive spectrum disorders have often revealed quite high levels of nail biting, among other habits. Only one trial of pharmacological agents has been described, in which clomipramine and desimipramine were compared in a double-blind, randomized study. A number of interventions have been proposed, but none has shown clear superiority in adequately designed trials.
Trasfondo médico en la novela "Madame Bovary" de Gustave Flaubert
AbstractOnychophagia, defined as habitual nail biting, is a common disorder affecting 20-30% of the population and all age groups. It may lead to significant psychosocial problems, have a negative impact on quality of life, and cause complications involving both the nail unit and the oral cavity. The objective of this paper is to review the prevalence, etiology, history, physical examination, complications and management of nail biting. Since onychophagia is a challenging disorder to treat, a multi-disciplinary approach should be taken involving dermatologists, internists, pediatricians, psychiatrists and dentists.
Evaluation and treatment of nail disorders utilizing practical nail surgical techniques
AbstractNail disorders frequently seen in daily practice may be inflammatory, infectious, tumoral, traumatic, or cicatricial. Surgical correction of the most common disorders is reviewed here. Treatment of the different types of ingrown nails as representative of the inflammatory diseases, the peculiarities in the treatment of an acute or a chronic hematoma, management of infectious diseases like chronic and acute paronychia, and different surgical techniques to treat a nail tumor depending where the problem is located, trying to prevent permanent postsurgical dystrophies are discussed.
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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