DeCure for Ehlers-Danlos syndrome due to tenascin-X deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Ehlers-Danlos syndrome due to tenascin-X deficiency — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEhlers-Danlos syndrome due to tenascin-X deficiency maps to a 3-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 ehlers-danlos syndrome due to tenascin-x deficiency 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
cytochrome P450 family 21 subfamily A member 2 (CYP21A2) — CYP21A2 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 hemdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4Y8W · 2.64 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). Experimental structure, not a prediction.
What the evidence adds up to
Tenascin-X deficiency causes a clinically distinct, recessive form of Ehlers-Danlos syndrome. In a 2001 study screening 151 EDS patients, 75 psoriasis patients, 93 rheumatoid arthritis patients, and 21 healthy persons, tenascin-X was absent from the serum of only 5 unrelated EDS patients. All five had hypermobile joints, hyperelastic skin, and easy bruising, but without atrophic scarring. Tenascin-C and type V collagen expression were normal in these patients. Tenascin-X mutations were identified in all five: one had a homozygous gene deletion, one was heterozygous for the deletion, and three had homozygous truncating point mutations.
The phenotype resembles the classical type of EDS but inheritance is autosomal recessive and wound healing is normal, so no atrophic scars are present. A 2011 report described four additional cases to improve clinical recognition, noting that because this type is rare and not included in the current diagnostic criteria, diagnosis is often delayed or overlooked. A 2019 report described one more patient with a homozygous null-mutation in the TNXB gene. Cellular characterisation showed a distinct organisation of the extracellular matrix, with normal deposition of fibronectin and normal organisation of the α5β1 integrin, distinguishing it from most other EDS subtypes.
No treatment or intervention was tested in any of these studies. What is still missing is any clinical trial data, any investigation of therapies, and any systematic patient stratification beyond case reports. The natural history and progression of this rare recessive form remain poorly quantified, and no funding or trial design for a drug-repurposing study has been reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2001 · 391 citations · open access
A Recessive Form of the Ehlers–Danlos Syndrome Caused by Tenascin-X Deficiency
AbstractBACKGROUND: The Ehlers-Danlos syndrome is a heritable connective-tissue disorder caused by defects in fibrillar-collagen metabolism. Mutations in the type V collagen genes account for up to 50 percent of cases of classic Ehlers-Danlos syndrome, but many other cases are unexplained. We investigated whether the deficiency of the tenascins, extracellular-matrix proteins that are highly expressed in connective tissues, was associated with the Ehlers-Danlos syndrome. METHODS: We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers-Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. We examined the expression of tenascins and type V collagen in skin by immunohistochemical methods and sequenced the tenascin-X gene. RESULTS: Tenascin-X was present in serum from all normal subjects, all patients with psoriasis, all patients with rheumatoid arthritis, and 146 of 151 patients with the Ehlers-Danlos syndrome. Tenascin-X was absent from the serum of the 5 remaining patients with Ehlers-Danlos syndrome, who were unrelated. Tenascin-X deficiency was confirmed in these patients by analysis of skin fibroblasts and by immunostaining of skin. The expression of tenascin-C and type V collagen was normal in these patients. All five of these patients had hypermobile joints, hyperelastic skin, and easy bruising, without atrophic scarring. Tenascin-X mutations were identified in all tenascin-X-deficient patients; one patient had a homozygous tenascin-X gene deletion, one was heterozygous for the deletion, and three others had homozygous truncating point mutations, confirming a causative role for tenascin-X and a recessive pattern of inheritance. CONCLUSIONS: Tenascin-X deficiency causes a clinically distinct, recessive form of the Ehlers-Danlos syndrome. This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix.
Well-defined clinical presentation of Ehlers–Danlos syndrome in patients with tenascin-X deficiency
AbstractThe Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of inherited connective tissue disorders. The six major, well-defined, subtypes are classified according to diagnostic criteria, formalized in the Villefranche revised nosology. Shortly after the publication of these criteria in 1998, a further distinct type of EDS, the tenascin-X (TNX)-deficient type EDS, was reported. The phenotype of this largely unknown type of EDS resembles the phenotype of the classical type of EDS, but its inheritance is autosomal recessive and wound healing is normal; hence, no atrophic scars are present. The clinical diagnosis can be confirmed by the absence of TNX in the serum and by mutation analysis of the TNXB gene. Because the TNX-deficient type EDS is rare and not included in the current diagnostic criteria, this diagnosis is often delayed or even overlooked. Here, we describe four cases which improve the clinical recognition of this type of EDS.
Clinical and Molecular Characterization of Classical-Like Ehlers-Danlos Syndrome Due to a Novel TNXB Variant
AbstractThe Ehlers-Danlos syndromes (EDS) constitute a clinically and genetically heterogeneous group of connective tissue disorders. Tenascin X (TNX) deficiency is a rare type of EDS, defined as classical-like EDS (clEDS), since it phenotypically resembles the classical form of EDS, though lacking atrophic scarring. Although most patients display a well-defined phenotype, the diagnosis of TNX-deficiency is often delayed or overlooked. Here, we described an additional patient with clEDS due to a homozygous null-mutation in the TNXB gene. A review of the literature was performed, summarizing the most important and distinctive clinical signs of this disorder. Characterization of the cellular phenotype demonstrated a distinct organization of the extracellular matrix (ECM), whereby clEDS distinguishes itself from most other EDS subtypes by normal deposition of fibronectin in the ECM and a normal organization of the α5β1 integrin.
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.
