DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant osteopetrosis 1 — 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 moduleAutosomal dominant osteopetrosis 1 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 autosomal dominant osteopetrosis 1 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 single case report describes a man with autosomal dominant osteopetrosis type II who later developed rheumatoid arthritis at age 42. Despite severe inflammation and rapid cartilage destruction, the progression of bone erosion was slow, which the authors attribute to the underlying defect in bone resorption. A separate case report describes a 14-year-old asymptomatic girl with autosomal dominant type II osteopetrosis, but provides no treatment or outcome data beyond confirming the diagnosis.
Whole exome sequencing of a cohort of osteopetrosis patients identified mutations in LRP5 in four patients with autosomal dominant osteopetrosis type I (ADOI) and mutations in CLCN7 in patients with type II (ADOII). In autosomal recessive osteopetrosis, TCIRG1 was the most frequently mutated gene; mutations were also found in FERMT3 and USB1. The study demonstrated that four deep intronic mutations and two synonymous changes in TCIRG1 and CLCN7 can cause disease. One patient initially thought to have osteopetrosis was found instead to carry a mutation in FAM20C, which causes Raine syndrome, illustrating the value of exome sequencing for differential diagnosis.
No clinical trial of any drug for autosomal dominant osteopetrosis is reported in these abstracts. No treatment, response rate, or survival data are given. The evidence is limited to genetic diagnosis and a single observation that bone erosion was slow in one patient with coincident rheumatoid arthritis.
What is still missing is any clinical trial testing a drug for this condition, any patient stratification beyond genetic mutation type, and any funding for such a trial. The natural history of bone density and fracture risk in untreated patients remains poorly quantified.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Modern Rheumatology · 2009 · 16 citations
Rheumatoid arthritis associated with osteopetrosis
AbstractOsteopetrosis is an inherited disorder characterized by reduced bone resorption. We here report a rare case of osteopetrosis associated with rheumatoid arthritis. The patient was diagnosed as autosomal dominant osteopetrosis type II in his youth and developed rheumatoid arthritis at 42 years of age. In spite of the severe inflammation and rapid progression of cartilage destruction, the progression of bone erosion was slow in this patient.
TAJ Journal of Teachers Association · 2009 · 0 citations · open access
Autosomal Dominant Type II Osteopctrosis in an Asymptomatic Adolescent: A Case Report
AbstractOsteopetrosis is a heterogeneous group of heritable conditions in which there is a defect in bone resorption by osteoclasts. The disease has variable mode of inheritance with variable expression of severity. We are reporting a 14 year old asymptomatic girl with autosomal dominant type II osteopetrosis and then the literature is reviewed.TAJ 2009; 22(1): 251-254
Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) · 2018 · 0 citations · open access
NEW INSIGHTS IN BONE BIOLOGY FROM EXOME SEQUENCING OF RARE SKELETAL DISEASES
AbstractWhole exome sequencing (WES) is a powerful tool to identify new molecules involved in skeletal homeostasis. In particular we used WES to establish the molecular diagnosis of two particular skeletal diseases: osteopetrosis and the acrofrontofacionasal dysostosis 1 (AFFND1). The osteopetroses are a group of rare bone diseases characterized by increased bone density due to the failure in bone resorption. Due to their genetic heterogeneity, WES represents a valuable strategy to identify the genetic defect. We analyzed osteopetrotic patients with autosomal dominant osteopetrosis (ADO) and autosomal recessive osteopetrosis (ARO), which is the most severe form. In our cohort we performed molecular diagnosis of 4 ADOI or ADOII patients that carried mutations in the LRP5 and CLCN7 genes, respectively. The analysis of ARO patients confirmed TCIRG1 as the most frequently mutated gene, identified mutations in the other known ARO genes and in genes very rarely associated with osteopetrosis, namely FERMT3 and USB1. Of note, we demonstrated the causative role of four deep intronic mutations in TCIRG1 gene and two different synonymous changes in the TCIRG1 and CLCN7 genes in the pathogenesis of the disease. In addition, WES helped in the differential diagnosis in a patient who was found to bear a mutation in the FAM20C gene, known to cause Raine syndrome. Regarding AFFND1, this is an extremely rare syndrome, comprising facial and skeletal abnormalities, short stature and intellectual disability. WES found a novel truncating mutation in the neuroblastoma-amplified sequence (NBAS) gene in two Indian patients (c.6237-3C>G). This mutation impaired NBAS functions in HEK293T cells overexpressing the truncated NBAS protein. Furthermore, we demonstrated that NBAS expression in mouse embryos was compatible with a role in bone and brain development and that the depletion of endogenous z-nbas in fish embryos resulted in defective morphogenesis of chondrogenic cranial skeletal elements. Overall, we provided evidence supporting the hypothesis of a causative role of the mutated NBAS gene in the pathogenesis of AFFND1. In conclusion, we effectively exploited WES in the genetic diagnosis of rare skeletal diseases. We also highlighted potential limitations of this approach, specifically with respect to deep intronic mutations and synonymous changes, and underlined the importance to complement WES with analysis at the transcript level and functional validation, when possible.
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.
