DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for vertebral column disorder — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleVertebral column disorder maps to a 35-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 vertebral column disorder 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
parvin alpha (PARVA) — PARVA 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 4rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2VZC · 1.05 Å · ligand (4R)-2-METHYLPENTANE-2,4-DIOL (MRD). Experimental structure, not a prediction.
What the evidence adds up to
Mice with one inactivated copy of the Col2a1 gene showed shorter limb bones, skulls, and spines at one month old, along with thicker and more irregular vertebral endplates that calcified earlier than controls. They also had lower glycosaminoglycan concentrations in the anulus fibrosus, endplates, and vertebral bone. These differences were compensated by 15 months, though long bones and skulls remained shorter. The gene-deficient mice used running wheels less, and physical exercise did not produce marked skeletal changes. The authors note that these early manifestations bear some resemblance to human spine disorders.
In a retrospective study of 78 patients with 125 spine metastases treated with stereotactic body radiotherapy at doses of 16 or 18 Gy, progressive disease was reported in 3.2% of cases at first PET/CT and 8.2% at last monitoring. Complete response was seen in 30.6% of patients initially and 62.3% at last follow-up; partial response in 47.1% initially and 16.7% at last follow-up; stable disease in 22.3% initially and 21% at last follow-up. Local failures occurred in 12% of cases. Grade 3 vertebral compression fractures developed in 4% of patients at a median of 16 months after SBRT. No bisphosphonate usage was significantly associated with VCF (r = −0.204; p = 0.022). Median fracture-free survival was 21 months. Female gender, bisphosphonate use, more than six months of bisphosphonate use, and the lowest vertebral body collapse score were associated with longer FFS on univariate analysis; female gender, more than six months of bisphosphonate use, and lowest collapse score retained independent significance.
A separate retrospective study of 53 patients treated with expandable titanium cages after vertebrectomy for malignant destruction, traumatic fracture, or osteoporotic fracture reported a mean operation time of 173.2 minutes. No implant-related complications occurred intraoperatively. Perioperative complications appeared in 34.0% of patients, with four severe cases and two deaths. During follow-up, 16 patients died, 10 of them due to tumour progression. Pain reduction was reported in 52.7% of patients and neurological improvement in 48.0%. One patient had loosening of posterior instrumentation due to tumour growth with cage dislocation and neurological deterioration. The authors conclude that sufficient stabilisation, pain reduction, and neurological improvement can be achieved with acceptable perioperative risk.
What remains missing is prospective trial data comparing these interventions against non-surgical management or placebo, standardised patient stratification by underlying pathology and spinal instability scores, and long-term follow-up beyond two years in adequately powered cohorts. No drug is mentioned in any of these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Spine · 2001 · 93 citations
Premature Vertebral Endplate Ossification and Mild Disc Degeneration in Mice After Inactivation of One Allele Belonging to the Col2a1 Gene for Type II Collagen
AbstractSTUDY DESIGN: Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied. OBJECTIVE: To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration. SUMMARY OF BACKGROUND DATA: Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown. METHODS: Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice. RESULTS: As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton. CONCLUSION: Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.
Journal of bone oncology · 2019 · 33 citations · open access
Local control and vertebral compression fractures following stereotactic body radiotherapy for spine metastases
AbstractWe aimed to retrospectively assess the incidence of vertebral compression fractures (VCF), examine clinicopathologic factors potentially associated with VCF, and evaluate treatment response in patients who received stereotactic body radiotherapy (SBRT) for spine metastases (spMets). We identified 78 patients with 125 spMets at baseline and subsequent assessments. Patients received SBRT doses of 16 or 18 Gy. Patients with pre-existing VCF and co-existing local progression were excluded. Spine instability neoplastic score (SINS) was used for spMets categorization. Response to SBRT and VCF were assessed according to the Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) and Genant scores, respectively. Kaplan–Meier analyses were used to assess local control of disease and vertebral compression fracture-free survival (FFS). We treated 103 cases with single spMets and 11 cases involving double spMets with SBRT. Progressive disease was reported in 3.2% and 8.2% of the cases in the first and last PET/CT reports, respectively. The distribution of treatment response in the remaining patients was: complete response in 30.6% of patients, partial response in 47.1% of patients, and stable disease in 22.3% of patients in the first PET/CT; complete response in 62.3% of patients, partial response in 16.7% of patients, and stable disease in 21% of patients at the last monitoring. Local failures were observed in 15 (12%) of cases. Median SINS was 5 (range: 1−13); majority of patients in our cohort (70.4%) were categorized as stable according to SINS, five (4%) patients had Grade 3 VCF at a median time of 16 months after SBRT (range: 2−22 months), and 60% of VCF occurred after an interval of at least 12 months after SBRT. No bisphosphonate usage was significantly associated with VCF (r = −0.204; p = 0.022). Median FFS was 21 months. Univariate analyses indicated that female gender (p < 0.001), bisphosphonate use (p = 0.005), >6 months of bisphosphonates use (p = 0.002), and the lowest vertebral body collapse score (p = 0.023) were associated with higher FFS. Female gender (p = 0.007), >6 months of bisphosphonates usage (p = 0.018), and the lowest vertebral body collapse score (p = 0.044) retained independent significance. This study demonstrated that spine SBRT with doses of 16–18 Gy promises good local control of disease with acceptable VCF rates. Lowest vertebral body collapse score, female gender, and >6 months of bisphosphonate use were significantly associated with longer FFS.
Zeitschrift für Orthopädie und ihre Grenzgebiete · 2004 · 12 citations
Wirbelkörperersatz durch expandierbare Titan-Cages
AbstractOBJECTIVES: The aim of vertebral body replacement is the stabilisation and restoration of the anterior column of the spine with removal of the diseased region. We present our results of stabilisation, pain reduction and neurological improvement using vertebral-body replacement systems METHODS: Between April 1997 and December 2002, 53 patients with malignant vertebral destruction or instability due to traumatic and osteoporotic fracture were treated. We evaluated the results after vertebrectomy and vertebral body replacement by using expandable titanium cages in a retrospective study. RESULTS: The average follow-up time was 18.9 +/- 19.9 months. The mean operation time was 173.2 +/- 77.4 minutes. Intraoperatively, we saw no implant-related complications. Perioperatively, complications appeared in 18 patients (34.0 %). 4 of them were severe, with 2 patients dying. In the total follow-up, 16 patients died, 10 of them (62.5 %) due to tumour progression. Pain reduction was reported in 52.7 %, neurological improvement in 48.0 %. One patient had a loosening of his posterior instrumentation in the further follow-up due to tumour growth with dislocation of the cage and a deterioration of his neurological deficit. CONCLUSION: By using vertebral body replacement systems, sufficient stabilisation of the vertebral column, pain reduction and neurological improvement can be achieved with an acceptable perioperative risk.
Abstract<b>Copyright information:</b>Taken from "The vertebral body growth plate in scoliosis: a primary disturbance of growth?"http://www.scoliosisjournal.com/content/3/1/3Scoliosis 2008;3():3-3.Published online 26 Jan 2008PMCID:PMC2253511. ×100. Mildly disordered columns of chondrocytes in the vertebral body growth plate in neurofibromatosis patient # 11.
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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