DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for osteogenesis imperfecta type 1 — screening already-approved drugs against its 5-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 1 maps to a 5-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 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.
Molecular view
prolyl 4-hydroxylase subunit beta (P4HB) — P4HB 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I7S · 2.5 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
Osteogenesis imperfecta type 1 is caused by mutations in the COL1A1 and COL1A2 genes that encode the alpha chains of collagen type I, according to a 2021 case report. A 2014 review notes that most cases of osteogenesis imperfecta are due to autosomal dominant type I collagen defects, while rare recessive forms arise from defects in genes whose protein products interact with collagen. These include bone-restricted IFITM-like protein (BRIL) and pigment epithelium-derived factor (PEDF) causing types V and VI via defective bone mineralization; CRTAP, P3H1, and cyclophilin B causing types VII–IX via defective collagen post-translational modification; HSP47 and FKBP65 causing types X and XI via aberrant collagen crosslinking; and SP7, WNT1, TRIC-B, and OASIS disrupting osteoblast development. Absence of BMP1 causes type XII due to altered collagen maturation.
A 2013 article similarly describes the pathophysiology of osteogenesis imperfecta, noting that historically it was considered a collagen-related condition predominantly due to mutations in collagen type I alpha chain genes, but mutations in various noncollagenous genes have more recently been discovered to cause some forms. The 2014 review states that identification of these multiple causative defects has provided information for genetic counselling and inspired a proposed functional grouping of osteogenesis imperfecta types by shared mechanism, and has prompted investigations into common pathways that could yield insight into clinical therapies.
A 2016 Spanish-language study examined the educational inclusion experience of a university student with osteogenesis imperfecta in a physical education course. The study found the student experienced stigmatisation personally and academically, and that future teachers expressed ignorance and insecurity about the disease and how to achieve inclusive treatment. Adaptations made by the instructor to ensure inclusion were described.
A 2021 case report describes implant-prosthetic restoration in a patient with type I osteogenesis imperfecta. It notes that only a few case reports of such treatment exist, and that implants and augmentation procedures can be implemented, but for patients receiving additional antiresorptive therapy, cautious approaches should be chosen and the risk of drug-associated osteonecrosis considered. No controlled trials of any drug therapy for osteogenesis imperfecta type 1 are reported in these abstracts. What is missing are randomised trials testing any pharmacological intervention specifically in type 1 OI, adequate patient stratification by genetic subtype, and funding for such studies.
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.
Estudios pedagógicos · 2016 · 10 citations · open access
Osteogénesis imperfecta y educación física: Un caso inédito de inclusión educativa
AbstractEl objetivo principal de este trabajo es indagar en la experiencia de inclusión educativa vivida por una alumna con osteogénesis imperfecta y por sus compañeras en una asignatura universitaria con contenidos relacionados con la educación física. La recogida de datos sobre la experiencia se realizó a lo largo de un cuatrimestre a partir de conversaciones informales con el profesor, entrevistas en profundidad y semi-estructuradas, y un cuestionario de respuesta abierta. El estudio revela la estigmatización sufrida por la alumna, tanto a nivel personal como académico (sobre todo en las clases de educación física) y el desconocimiento e inseguridad que manifiesta tener el futuro profesorado sobre esta enfermedad y cómo realizar un tratamiento inclusivo en sus clases. Asimismo, se describen las adaptaciones realizadas por el profesor de la asignatura con el fin de garantizar y ejemplificar la inclusión de una alumna con osteogénesis imperfecta en las clases de educación física.
International Journal of Environmental Research and Public Health · 2021 · 3 citations · open access
Implant-Prosthetic Restoration of a Patient with Osteogenesis Imperfecta: A Case Report
AbstractOsteogenesis imperfecta describes a group of genetic disorders that result from a defect in collagen type I and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Osteogenesis imperfecta is mostly caused by mutations in the COL1A1 (17q21.33) and COL1A2 (7q21.3) genes. There have only been a few case reports of implant-prosthetic treatment for patients with osteogenesis imperfecta. These reports indicated that implants and augmentation procedures can be implemented in such patients. However, for patients receiving additional antiresorptive therapy, cautious approaches should be chosen and the risk of drug-associated osteonecrosis should be considered. The aim of this article is to report on the implant-prosthetic treatment of a patient with type I osteogenesis imperfecta.
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.
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