DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spinal stenosis — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSpinal stenosis maps to a 41-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 spinal stenosis 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
RAB28, member RAS oncogene family (RAB28) — RAB28 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 g3ddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2HXS · 1.1 Å · ligand GUANOSINE-3'-MONOPHOSPHATE-5'-DIPHOSPHATE (G3D). Experimental structure, not a prediction.
What the evidence adds up to
In the Spine Patient Outcomes Research Trial, 289 patients were randomised to surgery or nonoperative care for lumbar spinal stenosis, with a further 365 enrolled in an observational cohort. An as-treated analysis combining both cohorts and adjusting for confounders found that the early advantages of surgery were maintained through four years: the treatment effect for bodily pain was 12.6 (95% CI 8.5–16.7), for physical function 8.6 (95% CI 4.6–12.6), and for the Oswestry Disability Index −9.4 (95% CI −12.6 to −6.2). Data were supplied by 67% to 89% of enrollees at each follow-up interval.
By eight years, data were obtained for 55% of the randomised group and 52% of the observational group. In the randomised cohort, 70% of those assigned to surgery and 52% of those assigned to nonoperative care had undergone surgery. As-treated analysis of the randomised group showed that the early benefit of surgery converged over time, with no significant treatment effect seen in years six to eight for any primary outcome. In contrast, the observational cohort maintained a stable advantage for surgery across all outcomes between years five and eight. Patients lost to follow-up were older, less educated, sicker, and had worse outcomes during the first two years in both arms, which could lead to overestimates of long-term outcomes.
A systematic review and meta-analysis of 19 reports from 17 randomised trials found no trials comparing surgery to no treatment or placebo. Decompression plus fusion was not superior to decompression alone for pain (mean difference −3.7, 95% CI −15.6 to 8.1), disability (mean difference 9.8, 95% CI −9.4 to 28.9), or walking ability (risk ratio 0.9, 95% CI 0.4 to 1.9). Interspinous process spacer devices were slightly more effective than decompression plus fusion for disability (mean difference 5.7, 95% CI 1.3 to 10.0), but resulted in significantly higher reoperation rates (28% versus 7%, P < 0.001). The relative efficacy of various surgical options remains uncertain.
What is still missing is a placebo-controlled or sham-surgery trial that could separate the specific effect of surgery from the natural history and regression to the mean. The high crossover rates in the randomised trial and the differential loss to follow-up of sicker patients make the long-term results difficult to interpret. No trial has identified which patient subgroups, if any, derive durable benefit beyond four years, and no non-surgical drug therapy has been tested against surgery in a randomised design for this condition.
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 · 2010 · 589 citations
Surgical Versus Nonoperative Treatment for Lumbar Spinal Stenosis Four-Year Results of the Spine Patient Outcomes Research Trial
AbstractIn Brief Study Design. Randomized trial and concurrent observational cohort study. Objective. To compare 4 year outcomes of surgery to nonoperative care for spinal stenosis. Summary of Background Data. Surgery for spinal stenosis has been shown to be more effective compared to nonoperative treatment over 2 years, but longer-term data have not been analyzed. Methods. Surgical candidates from 13 centers in 11 US states with at least 12 weeks of symptoms and confirmatory imaging were enrolled in a randomized cohort (RC) or observational cohort (OC). Treatment was standard decompressive laminectomy or standard nonoperative care. Primary outcomes were SF-36 bodily pain (BP) and physical function scales and the modified Oswestry Disability index assessed at 6 weeks, 3 months, 6 months, and yearly up to 4 years. Results. A total of 289 patients enrolled in the RC and 365 patients enrolled in the OC. An as-treated analysis combining the RC and OC and adjusting for potential confounders found that the clinically significant advantages for surgery previously reported were maintained through 4 years, with treatment effects (defined as mean change in surgery group minus mean change in nonoperative group) for bodily pain 12.6 (95% confidence interval [CI], 8.5–16.7); physical function 8.6 (95% CI, 4.6–12.6); and Oswestry Disability index −9.4 (95% CI, −12.6 to −6.2). Early advantages for surgical treatment for secondary measures such as bothersomeness, satisfaction with symptoms, and self-rated progress were also maintained. Conclusion. Patients with symptomatic spinal stenosis treated surgically compared to those treated nonoperatively maintain substantially greater improvement in pain and function through 4 years. Four-year outcomes for the Spine Patient Outcomes Research Trial spinal stenosis surgical and nonoperative cohorts are reported. Overall, 419 patients received surgery at some point during the first 4 years; 235 remained nonoperative. The proportion of enrollees who supplied data at each follow-up visit interval ranged from 67% to 89% with losses due to dropouts, missed visits, or deaths. The as-treated analysis combining the randomized and observational cohorts and adjusting for potential confounders found that the clinically significant advantages for surgery previously reported were maintained through 4 years.
Clinical Orthopaedics and Related Research · 1992 · 308 citations
The Natural Course of Lumbar Spinal Stenosis
AbstractThe course of 32 untreated patients with spinal stenosis was studied. The mean patient age was 60 years, and the mean period of observation was 49 months. About 75% of the patients had spinal claudication. In the follow-up survey, the same number of patients had claudication, but the symptoms were milder. In estimation by visual analog scale, symptoms in 70% of the cases were unchanged, 15% showed improvement, and 15% worsened. No proof of severe deterioration was found after four years, and expectant observation may be an alternative to surgical treatment.
AbstractIn Brief Study Design. Randomized trial with a concurrent observational cohort study. Objective. To compare 8-year outcomes of surgery with nonoperative care for symptomatic lumbar spinal stenosis. Summary of Background Data. Surgery for spinal stenosis has been shown to be more effective than nonoperative treatment during 4 years, but longer-term data are less clear. Methods. Surgical candidates from 13 centers in 11 US states with at least 12 weeks of symptoms and confirmatory imaging were enrolled in a randomized cohort or observational cohort. Treatment was standard, decompressive laminectomy versus standard nonoperative care. Primary outcomes were SF-36 (MOS 36-Item Short-Form Health Survey) Bodily Pain and Physical Function scales and the modified Oswestry Disability Index assessed at 6 weeks, 3 months, 6 months, and yearly up to 8 years. Results. Data were obtained for 55% of participants in the randomized group and 52% of participants in the observational group at the 8-year follow-up. Intent-to-treat analyses showed no differences between randomized cohorts; however, 70% of those randomized to surgery and 52% of those randomized to nonoperative had undergone surgery by 8 years. As-treated analyses in the randomized group showed that the early benefit for surgery out to 4 years converged over time, with no significant treatment effect of surgery seen in years 6 to 8 for any of the primary outcomes. In contrast, the observational group showed a stable advantage for surgery in all outcomes between years 5 and 8. Patients who were lost to follow-up were older, less well-educated, sicker, and had worse outcomes during the first 2 years in both surgical and nonoperative arms. Conclusion. Patients with symptomatic spinal stenosis show diminishing benefits of surgery in as-treated analyses of the randomized group between 4 and 8 years, whereas outcomes in the observational group remained stable. Loss to follow-up of patients with worse early outcomes in both treatment groups could lead to overestimates of long-term outcomes but likely not bias treatment effect estimates. Level of Evidence: 1 Eight-year outcomes for the SPORT lumbar spinal stenosis (SpS) surgical and nonoperative cohorts are reported. Overall, 428 patients with SpS underwent surgery at some point during the first 8 years; 226 remained nonoperative. The as-treated analyses in the randomized cohort showed convergence in outcomes over time with no significant advantage to surgery at 6 to 8 years, whereas in the observational cohort, the significant advantages for surgery previously reported were maintained through 8 years.
Effectiveness of Surgery for Lumbar Spinal Stenosis: A Systematic Review and Meta-Analysis
AbstractBACKGROUND: The management of spinal stenosis by surgery has increased rapidly in the past two decades, however, there is still controversy regarding the efficacy of surgery for this condition. Our aim was to investigate the efficacy and comparative effectiveness of surgery in the management of patients with lumbar spinal stenosis. METHODS: Electronic searches were performed on MEDLINE, EMBASE, AMED, CINAHL, Web of Science, LILACS and Cochrane Library from inception to November 2014. Hand searches were conducted on included articles and relevant reviews. We included randomised controlled trials evaluating surgery compared to no treatment, placebo/sham, or to another surgical technique in patients with lumbar spinal stenosis. Primary outcome measures were pain, disability, recovery and quality of life. The PEDro scale was used for risk of bias assessment. Data were pooled with a random-effects model, and the GRADE approach was used to summarise conclusions. RESULTS: Nineteen published reports (17 trials) were included. No trials were identified comparing surgery to no treatment or placebo/sham. Pooling revealed that decompression plus fusion is not superior to decompression alone for pain (mean difference -3.7, 95% confidence interval -15.6 to 8.1), disability (mean difference 9.8, 95% confidence interval -9.4 to 28.9), or walking ability (risk ratio 0.9, 95% confidence interval 0.4 to 1.9). Interspinous process spacer devices are slightly more effective than decompression plus fusion for disability (mean difference 5.7, 95% confidence interval 1.3 to 10.0), but they resulted in significantly higher reoperation rates when compared to decompression alone (28% v 7%, P < 0.001). There are no differences in the effectiveness between other surgical techniques for our main outcomes. CONCLUSIONS: The relative efficacy of various surgical options for treatment of spinal stenosis remains uncertain. Decompression plus fusion is not more effective than decompression alone. Interspinous process spacer devices result in higher reoperation rates than bony decompression.
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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