DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for osteogenesis imperfecta type 10 — 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 moduleOsteogenesis imperfecta type 10 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 osteogenesis imperfecta type 10 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
Osteogenesis imperfecta type 10 is not mentioned by name in any of the provided abstracts. The abstracts discuss osteogenesis imperfecta generally, noting that the disorder is caused by mutations in COL1A1 or COL1A2 in most patients, and that mutations in at least 20 other genes can also lead to the disease. Two new genes, CRTAP and LEPRE1, were identified in patients with recessive severe or lethal forms. The 2023 abstract summarises pathogenic mechanisms including type I collagen defects, bone mineralisation disorders, and osteoblast differentiation defects, and states that the previous classifications lack structure and scientific basis.
Regarding treatment, a 1981 review found that 70% of published articles on medical treatment claimed beneficial results for 20 different agents, but concluded that no agent was available that would be of any value to the practitioner. A 2009 review states that bisphosphonates have been accepted as standard of care for children with osteogenesis imperfecta, but notes that questions remain about patient selection, effectiveness in fracture prevention, which bisphosphonate to use, and duration of treatment. Two recent reports cited in that review document the paucity of evidence-based data regarding the effectiveness of bisphosphonate treatment in fracture prevention. A 2012 review calls bisphosphonate treatment the most important therapeutic advance for moderate to severe forms, but states that the best regimen and long-term outcomes are unknown, and that the treatment does not constitute a cure. A 2021 review describes current treatment as symptomatic and states that the search for new treatment strategies continues.
No abstract reports a clinical trial, survival data, or response rates for any drug in osteogenesis imperfecta type 10 or any other subtype. What is missing is any trial that tests a drug specifically in patients with a confirmed genetic diagnosis of type 10, any evidence that bisphosphonates or other agents alter the natural history of that particular subtype, and any validated outcome measure that distinguishes treatment effect from the disorder's variable course.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Pediatrics · 2009 · 92 citations
Osteogenesis imperfecta: questions and answers
AbstractPURPOSE OF REVIEW: Considerable attention has recently been focused on the pathogenesis, diagnosis and treatment of osteogenesis imperfecta. Two new genes have been defined in patients with recessive severe or lethal osteogenesis imperfecta types. Diagnostic concerns involve testing procedures, either skin biopsies or DNA analysis. Bisphosphonates have been accepted as 'standard of care' for children with osteogenesis imperfecta. However, questions remain as to the selection of patients for treatment, effectiveness in fracture prevention, which bisphosphonates should be used and the duration of treatment. Orthopedic intervention occurs on several levels: including the immediate treatment of fractures, the treatment of scoliosis and the use of intramedullary rods. RECENT FINDINGS: The discovery of mutations involving CRTAP and LEPRE1 genes in severe/lethal and recessively inherited osteogenesis imperfecta has provided partial answers to questions about 'other' osteogenesis imperfecta genes in patients with an osteogenesis imperfecta phenotype but no COL1A1 and COL1A2 mutations. Current experience suggests that DNA analysis is a better test for diagnosis as compared with dermal biopsy. There are no standardized guidelines for initiating bisphosphonate treatment in children. Recent data suggest either intravenous or oral bisphosphonates are effective, but differences exist between different bisphosphonates. Two recent reports document the paucity of evidence-based data regarding the effectiveness of bisphosphonate treatment in fracture prevention. SUMMARY: This report will update the medical and orthopedic approaches to care for children with osteogenesis imperfecta.
Clinical Orthopaedics and Related Research · 1981 · 40 citations
Systemic Treatment of Osteogenesis Imperfecta
AbstractSeventy percent of published articles on the medical treatment of osteogenesis imperfecta have claimed beneficial results for 20 different agents. This observation conflicts with current practice since no form of treatment has been accepted as effective in dealing with the disease. A few medications or combinations of medications hold some promise, but adequate documentation must be availble before they can be accurately assessed. It is essential that the practitioner maintain a high degree of skepticism toward positive results of treatment regardless of the source. At the present time, no agent is available which will be of any value to the practitioner who has a patient with osteogenesis imperfecta.
Orphanet Journal of Rare Diseases · 2023 · 25 citations · open access
Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification
AbstractOsteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and complex pathogenic mechanisms. The previous classifications lack structure and scientific basis and have poor applicability. In this paper, we summarize and sort out the pathogenic mechanisms of OI, and analyze the molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects(synthesis defects, processing defects, post-translational modification defects, folding and cross-linking defects), bone mineralization disorders, osteoblast differentiation and functional defects respectively, and also generalize several new untyped OI-causing genes and their pathogenic mechanisms, intending to provide the evidence of classification and a scientific basis for the precise diagnosis and treatment of OI.
AbstractOsteogenesis imperfecta is a genetic disorder of increased bone fragility, low bone mass, and other connective-tissue manifestations. The most frequently used classification outlines four clinical types, which we have expanded to seven distinct types. In most patients the disorder is caused by mutations in one of the two genes encoding collagen type 1, but in some individuals no such mutations are detectable. The most important therapeutic advance is the introduction of bisphosphonate treatment for moderate to severe forms of osteogenesis imperfecta. However, at present, the best treatment regimen and the long-term outcomes of bisphosphonate therapy are unknown. Although this treatment does not constitute a cure, it is an adjunct to physiotherapy, rehabilitation, and orthopaedic care. Gene-based therapy presently remains in the early stages of preclinical research.
Osteogenesis imperfecta: classification, clinical features, and treatment
AbstractOsteogenesis imperfecta (OI) is a monogenic disorder characterized by increased bone fragility and several extraskeletal manifestations. In most cases, OI is caused by mutations in one of the two genes encoding alpha chains of type I collagen, COL1A1 or COL1A2. Mutations in at least 20 other genes can also lead to OI. Clinical manifestation of the disease ranges from mild to severe form with possible perinatal lethality. The disease may significantly reduce patient’s quality of life, which requires timely and optimal treatment and a multidisciplinary approach. Currently, the therapeutic treatment of osteogenesis imperfecta is symptomatic, but the search for new treatment strategies aimed at preventing the risk of new fractures and the progression of bone deformity continues. Key words: аnabolic therapy, antiresorptive therapy, сollagen, osteogenesis imperfecta, fracture
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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