DeCure for Autosomal dominant osteosclerosis, Worth type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant osteosclerosis, Worth type — 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 dominant osteosclerosis, Worth type 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 dominant osteosclerosis, worth type 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
A 1987 review of radiographs from 26 patients with autosomal dominant osteopetrosis identified two distinct, family-related radiographic types. Both types showed universal osteosclerosis. Type 1 featured pronounced sclerosis of the cranial vault with the spine almost unaffected. Type 2 had sclerosis most pronounced at the skull base, consistent end-plate thickening in the vertebrae, and convex arcs of sclerotic bone in the iliac wings. Age and sex distribution did not differ between the types. The authors concluded that autosomal dominant osteopetrosis may be a heterogeneous group of inherited bone disorders.
A 2013 case report described a 35-year-old woman with autosomal dominant osteopetrosis type II who presented with chronic generalised periodontitis. Radiographs showed generalised osteosclerosis and the hallmark features of ADO type II: a "bone-within-bone appearance" and "Erlenmeyer-flask deformity." The report noted that autosomal dominant osteopetrosis is the most common of the three recognised forms of the disease and typically has milder symptoms that often appear in later childhood or adulthood.
A 2024 report described three family members with a single heterozygous missense variant (p.Gly579Arg) in the TCIRG1 gene who had a phenotype consistent with autosomal dominant osteopetrosis. This is the first description of adult presentation of ADO caused by a TCIRG1 variant. Two subjects had severe disease and the third had very mild disease, demonstrating marked phenotypic variability similar to that seen in families with ADO from CLCN7 mutations. The report notes that TCIRG1 variants are commonly identified in autosomal recessive osteopetrosis but had previously been reported in only one patient with ADO. Three of five protein prediction programs suggested the variant likely inhibits TCIRG1 function.
No treatment or intervention was tested in any of these reports. What is still missing is any clinical trial data, any investigation of drug repurposing, any systematic patient stratification beyond radiographic typing, and any funding for prospective studies that could link specific genotypes to outcomes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Radiology · 1987 · 92 citations
Heterogeneity of autosomal dominant osteopetrosis.
AbstractA review of the radiographs of 26 patients with autosomal dominant osteopetrosis disclosed two distinct and strictly family-related radiographic types. Both types had universal osteosclerosis. In type 1 the most striking finding was pronounced sclerosis of the cranial vault while the spine was almost unaffected. In type 2 the sclerosis of the skull was most pronounced at the base, the vertebrae always had end-plate thickening, and in the pelvis the iliac wings contained convex arcs of sclerotic bone. Age and sex distribution did not differ between the types. Autosomal dominant osteopetrosis may be a heterogeneous group of inherited bone disorders.
Case Reports in Dentistry · 2013 · 17 citations · open access
Clinical and Radiological Findings of Autosomal Dominant Osteopetrosis Type II: A Case Report
AbstractOsteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton caused by the absence or malfunction of osteoclasts. Three distinct forms of the disease have been recognized, autosomal dominant osteopetrosis being the most common. Autosomal dominant osteopetrosis exhibits a heterogeneous trait with milder symptoms, often at later childhood or adulthood. The aim of this case report is to present the clinical and radiographic features of a 35-year-old female patient with autosomal dominant osteopetrosis type II who exhibited features of chronic generalised periodontitis, and the radiographs revealed generalised osteosclerosis and hallmark radiographic features of ADO type II, that is, "bone-within-bone appearance" and "Erlenmeyer-flask deformity."
The Journal of Clinical Endocrinology & Metabolism · 2024 · 7 citations · open access
Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the <i>TCIRG1</i> Gene
AbstractCONTEXT: Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or bone marrow failure. ADO usually results from heterozygous missense variants in the Chloride Channel 7 gene (CLCN7) that cause disease by a dominant negative mechanism. Variants in the T-cell immune regulator 1 gene (TCIRG1) are commonly identified in autosomal recessive osteopetrosis but have only been reported in 1 patient with ADO. CASE DESCRIPTION: Here, we report 3 family members with a single heterozygous missense variant (p.Gly579Arg) in TCIRG1 who have a phenotype consistent with ADO. Three of 5 protein prediction programs suggest this variant likely inhibits the function of TCIRG1. CONCLUSION: This is the first description of adult presentation of ADO caused by a TCIRG1 variant. Similar to families with ADO from CLCN7 mutations, this variant in TCIRG1 results in marked phenotype variability, with 2 subjects having severe disease and the third having very mild disease. This family report implicates TCIRG1 missense mutations as a cause of ADO and demonstrates that the marked phenotypic variability in ADO may extend to disease caused by TCIRG1 missense mutations.
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.
