Rare & Orphan Lab · DeCure for X
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for pachyonychia congenita — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
No approved-drug candidate for pachyonychia congenita 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.
keratin 10 (KRT10) — KRT10 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.
RCSB Protein Data Bank · entry 6UUI · 2.069 Å · ligand octyl beta-D-glucopyranoside (BOG). Experimental structure, not a prediction.
Pachyonychia congenita is a rare hereditary skin disorder caused by a mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. In a Chinese Han family with pachyonychia congenita type 2, a heterozygous 296T→C mutation in KRT17 was found in all affected members, resulting in a leucine-to-proline substitution at codon 99 (L99P) in the 1A domain of the keratin 17 protein. This mutation was absent in unaffected family members and 100 unrelated healthy controls, suggesting it plays a major role in the pathogenesis of that pedigree. Clinical manifestations are variable and can include thickened nails, painful palmoplantar keratoderma, epidermal cysts, callosities of the feet with blistering, hyperhidrosis, unusual hair texture, and white lesions of the oral mucosa. One report describes three individuals across three successive generations of one family with pachyonychia congenita involving multiple nails of hands and feet, along with epidermal cysts and erupted teeth at birth.
A 2016 case report describes a child with pachyonychia congenita who also had bronchiectasis and renal artery stenosis, suggesting a possible syndromic association beyond the typical keratin gene mutations. Another report from 1937 describes a 20-year-old woman with persistent, foul-smelling erosive lesions on her feet that had failed to respond to innumerable types of therapy over seven years; the paper aimed to demonstrate the value of buffered cysteine hydrochloride in such lesions, but no efficacy data or outcomes are provided in the abstract. Pachyonychia congenita type 1, due to mutations in K6a or K16 keratins, can present with nail involvement that clinically resembles chronic mucocutaneous candidosis, a separate immune deficiency disorder.
The Pachyonychia Congenita Project is an international patient advocacy organisation that unites patients, researchers, physicians, and industry partners through the International Pachyonychia Congenita Consortium and the International Pachyonychia Congenita Research Registry to advance research and drug development. What remains missing are published clinical trial results for any specific drug therapy, adequate funding for rare-disease trials, and a clear stratification of patients by the specific keratin gene mutation, which may determine response to future treatments.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractThree individuals representing three successive generations of one family are presented demonstrating pachyonychia congenita involving multiple nails of hands and feet, epidermal cysts, callosities of feet with blistering, hyperhidrosis, unusual hair texture, and erupted teeth at birth.
https://doi.org/10.1001/archderm.97.1.31AbstractThe purpose of this paper is not to report a case of pachyonychia congenita of Jadassohn, which has been excellently described by Tauber, Goldman and Claassen,1Sohrweide,2Andrews and Strumwasser>3and Diasio,4or to summarize the thorough reports of Hammett and Reimann>5and Brunsting and Simonsen>6on the sulfhydryl groups, but to demonstrate the value of buffered cysteine hydrochloride in other conditions than ulcerated lesions. I wish to report here the progress of a girl, aged 20, previously presented by Tauber and his associates. She had had persistent and resistant foul-smelling erosive lesions for a period of seven years and the condition had failed to respond to innumerable types of therapy. Figure 1 shows the type of lesion which was present, not only on the lateral aspects of the feet, but also on the plantar and posterior portions in symmetrical fashion. The lesions were
https://doi.org/10.1001/archderm.1937.01480020087013AbstractPachyonychia Congenita Project (PC Project) is an international patient advocacy organization dedicated to patients who suffer from pachyonychia congenita (PC). This condition is a painful and debilitating skin disorder caused by a mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16,or KRT17. Through two primary programs, namely the International Pachyonychia Congenita Consortium (IPCC) and the International Pachyonychia Congenita Research Registry (IPCRR), PC Project provides comprehensive patient support and diagnostics while uniting patients, researchers, physicians, and industry partners on a global level to advance research and drug development for meaningful treatments and, ultimately, a cure for PC.
https://doi.org/10.2302/kjm.2023-0015-irAbstractPachyonychia congenita (PC) is a rare hereditary disease, mainly characterized by a painful palmoplantar keratoderma, thickened nails, cysts and white lesions of the oral mucosa. Its clinical manifestations are very variable, it may appear from birth to adulthood. This study report the case of a child with pachyonychia congenita associated with bronchiectasis and renal artery stenosis. The diagnosis of pachyonychia congenita was retained based on clinical and histological data. However the presence of renal artery stenosis and bronchiectasis suggests a possible association as part of a particular syndromic group.
https://doi.org/10.11604/pamj.2016.24.183.9284AbstractOBJECTIVE: To investigate the keratin 17 gene (KRT17) mutation in a pedigree with pachyonychia congenita type 2 (PC-II). METHODS: DNA was extracted from the blood samples of the patients, unaffected members of the pedigree, and 100 unrelated healthy controls. PCR was performed to amplify the hot spots in KRT17 gene. PCR products were directly sequenced to detect mutation. RESULTS: A heterozygous 296T-->C mutation was found in all the affected members of this family, which resulted in the substitution of leucine by proline in codon 99 (L99P) in the 1A domain of the KRT17, but not in the healthy individuals from the family and the 100 unrelated controls. CONCLUSION: The mutation of KRT17 may play a major role in the pathogenesis of this pedigree with pachyonychia congenita type 2.
https://doi.org/10.3760/cma.j.issn.1003-9406.2011.01.002AbstractPachyonychia congenita 1 (PC1) is an inherited skin disorder due to the mutation of a gene codifying for K6a and K16 keratins. Autosomal dominant chronic mucocutaneous candidosis is due to a primary immune deficiency. Although being very different diseases, the nail involvement in both of them can give rise clinically to diagnosis problems.
https://doi.org/10.26326/2281-9649.28.1.1637Disease 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.
