DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for osteogenesis imperfecta type 7 — 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 7 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 7 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
cartilage associated protein (CRTAP) — CRTAP 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…
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RCSB Protein Data Bank · entry 8K0M · 3.17 Å · ligand 2-OXOGLUTARIC ACID (AKG). Experimental structure, not a prediction.
What the evidence adds up to
Osteogenesis imperfecta type VII is a rare, recessive form of the disorder caused by defects in the gene for cartilage-associated protein (CRTAP), which leads to defective collagen post-translational modification. This classification was established by 2014, when a review noted that CRTAP defects cause types VII through IX osteogenesis imperfecta. The same review placed type VII among the non-collagenous gene forms that account for a minority of cases, while most osteogenesis imperfecta is due to autosomal dominant mutations in COL1A1 or COL1A2.
No clinical trial, case series, or animal study testing a specific drug for osteogenesis imperfecta type VII is reported in these abstracts. The 2021 review states that current treatment for osteogenesis imperfecta overall is symptomatic and that the search for new strategies continues. The 2013 and 2014 reviews describe the genetic mechanisms but provide no data on any pharmacological intervention for type VII or any other recessive form.
The 1987 paper on type IIA osteogenesis imperfecta, a different and lethal form, found that 30 radiologically proven cases were all isolated, with 19 unaffected foreborn and 19 unaffected afterborn siblings. Two sets of parents, both Asian, were consanguineous. There was a significant parental age effect, most marked for paternal age. The authors concluded that most cases of type IIA result from new dominant mutations.
What is missing for osteogenesis imperfecta type VII specifically is any preclinical or clinical drug testing, any patient cohort with measured outcomes, and any trial design. The genetic mechanism is known, but no compound has been evaluated in this subtype. Funding for drug screening in CRTAP-deficient models, development of patient-derived cell assays, and recruitment of the small number of affected individuals into natural history studies would be needed before any treatment could be tested.
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 · 2014 · 139 citations · open access
Osteogenesis imperfecta due to mutations in non-collagenous genes
AbstractPURPOSE OF REVIEW: Osteogenesis imperfecta or 'brittle bone disease' has mainly been considered a bone disorder caused by collagen mutations. Within the last decade, however, a surge of genetic discoveries has created a new paradigm for osteogenesis imperfecta as a collagen-related disorder, where most cases are due to autosomal dominant type I collagen defects, while rare, mostly recessive, forms are due to defects in genes whose protein products interact with collagen protein. This review is both timely and relevant in outlining the genesis, development, and future of this paradigm shift in the understanding of osteogenesis imperfecta. RECENT FINDINGS: Bone-restricted interferon-induced transmembrane (IFITM)-like protein (BRIL) and pigment epithelium-derived factor (PEDF) defects cause types V and VI osteogenesis imperfecta via defective bone mineralization, while defects in cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1), and cyclophilin B (CYPB) cause types VII-IX osteogenesis imperfecta via defective collagen post-translational modification. Heat shock protein 47 (HSP47) and FK506-binding protein-65 (FKBP65) defects cause types X and XI osteogenesis imperfecta via aberrant collagen crosslinking, folding, and chaperoning, while defects in SP7 transcription factor, wingless-type MMTV integration site family member 1 (WNT1), trimeric intracellular cation channel type b (TRIC-B), and old astrocyte specifically induced substance (OASIS) disrupt osteoblast development. Finally, absence of the type I collagen C-propeptidase bone morphogenetic protein 1 (BMP1) causes type XII osteogenesis imperfecta due to altered collagen maturation/processing. SUMMARY: Identification of these multiple causative defects has provided crucial information for accurate genetic counseling, inspired a recently proposed functional grouping of osteogenesis imperfecta types by shared mechanism to simplify current nosology, and has prodded investigations into common pathways in osteogenesis imperfecta. Such investigations could yield critical information on cellular and bone tissue mechanisms and translate to new mechanistic insight into clinical therapies for patients.
Journal of Medical Genetics · 1987 · 49 citations · open access
Osteogenesis imperfecta type IIA: evidence for dominant inheritance.
AbstractThirty cases of radiologically proven type IIA osteogenesis imperfecta (OI) have been ascertained. All were isolated with 19 unaffected foreborn and 19 unaffected afterborn sibs. Two sets of parents, both Asian, were consanguineous. There was a significant parental age effect, most marked for paternal age. It is concluded that most cases of type IIA OI result from new dominant mutations.
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
AbstractThis article discusses the pathophysiology of osteogenesis imperfecta (OI), in particular in relation to some rare, recessive forms of the condition. Although historically considered a collagen-related condition, predominantly due to mutations in genes that encode the alpha chains of collagen type I, mutations in various noncollagenous genes have also more recently been discovered to cause some forms of OI.
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.
