DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for radiculopathy — 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 moduleRadiculopathy 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 radiculopathy 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
prostaglandin-endoperoxide synthase 2 (PTGS2) — PTGS2 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 saldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5F1A · 2.38 Å · ligand 2-HYDROXYBENZOIC ACID (SAL). Experimental structure, not a prediction.
What the evidence adds up to
In a rat model, inflammation induced in a lumbar facet joint spread to nerve roots and produced mechanical allodynia from day 3, with gradual recovery over the observation period. Significantly more inflammatory cells infiltrated the epidural space on days 3 and 7, and numbers of TNF-alpha-immunoreactive cells in the dorsal root ganglion were significantly increased on days 1 and 3, predominantly in small nociceptive neurons. A separate rat study using nerve root ligation identified 16 upregulated genes in the dorsal root ganglion on day 2, 56 genes on days 7 and 14, and 17 genes upregulated continuously from day 2 to 21; functional categories shifted from transcription/translation to enzyme/metabolism to structure over time. The authors of that study noted these genes, particularly those involved in pain signalling and inflammation, as potential targets for molecular-based therapy.
A pilot investigation of 10 patients with lumbosacral radiculopathy treated with an indwelling epidural catheter delivering 8.0 mg dexamethasone over 72 hours reported no morbidity or mortality. Mean VAS improvement at six weeks was 4.1 (SD 2.6), with a mean percent improvement of 46.7%. A retrospective cohort study of patients undergoing revision lumbar microdiscectomy for radiculopathy between 2018 and 2022 found that over 92% of patients who had scarectomy alone reported improved pain scores, and the authors stated that complete resection of scar tissue alone appeared to yield similar VAS improvements to revision microdiscectomy for recurrent disc.
A prospective multicentre analysis of 1522 patients undergoing surgery for degenerative cervical pathology examined the impact of preoperative nonoperative treatments. Among 1319 radiculopathy patients, 25.7% received epidural injections, 35.3% physical therapy, and 35.5% opioids. Radiculopathy patients who received epidurals and physical therapy had higher 1-year return-to-work rates. Those who had physical therapy also had shorter hospital stays, greater SF-36 physical functioning and physical component score improvements, lower 2-year VAS neck/arm pain scores, and higher 2-year return-to-work incidence. Among 203 myelopathy patients, 14.8% received epidural injections, 25.1% opioids, and 41.5% physical therapy; myelopathy patients who had preoperative physical therapy had worse VAS arm pain scores at 2 years, and no nonoperative treatment was associated with return-to-work rate in that group.
What is still missing are large, randomised controlled trials comparing these interventions against sham or no treatment, particularly for the indwelling catheter and scarectomy approaches, which were studied in small, uncontrolled or retrospective cohorts. The animal models identify molecular targets but have not been translated into human therapies. Patient stratification by pathology type (radiculopathy versus myelopathy, or by specific inflammatory or structural findings) remains unaddressed in most studies, and funding for such stratified trials is lacking.
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 · 2007 · 53 citations
Does Facet Joint Inflammation Induce Radiculopathy?
AbstractSTUDY DESIGN: The association between lumbar facet joint inflammation and radiculopathy was investigated using behavioral, histologic, and immunohistochemical testing in rats. OBJECTIVES: To develop a rat model of lumbar facet joint inflammation and ascertain whether facet joint inflammation induces radiculopathy using this model. SUMMARY OF BACKGROUND DATA: Both mechanical and chemical factors have been identified as important for inducing radiculopathy. In lumbar spondylosis, facet joint osteophytes may contribute to nerve root compression, which may induce radiculopathy. Furthermore, inflammation may occur in the facet joint, as in other synovial joints. Inflamed synovium may thus release inflammatory cytokines and induce nerve root injury with subsequent radiculopathy. METHODS: A piece of gelatin sponge containing complete adjuvant was inserted into the L5-L6 facet joint in rats (arthritis group). Saline was used in the control group. Mechanical allodynia was determined using the von Frey test. Inflammatory cells infiltrating the epidural space were counted, and changes in cartilage were assessed histologically. Tumor necrosis factor (TNF)-alpha-immunoreactive cells in the L5 dorsal root ganglion were counted. RESULTS: Mechanical allodynia was observed in the arthritis group from day 3, gradually recovering during the observation period. Significantly larger numbers of inflammatory cells had infiltrated the epidural space by days 3 and 7 in the arthritis group than in controls. Numbers of TNF-alpha-immunoreactive cells were significantly increased at days 1 and 3 in the arthritis group compared with controls. Predominantly small nociceptive neurons were stained. CONCLUSIONS: When inflammation was induced in a facet joint, inflammatory reactions spread to nerve roots, and leg symptoms were induced by chemical factors. These results support the possibility that facet joint inflammation induces radiculopathy.
Gene Expression Profile of Dorsal Root Ganglion in a Lumbar Radiculopathy Model
AbstractSTUDY DESIGN: DNA array analysis of dorsal root ganglion (DRG) using a rat model with nerve root constriction. OBJECTIVE: To determine the molecular changes in the DRG adjacent to the injured nerve root in a lumbar radiculopathy model. SUMMARY OF BACKGROUND DATA: DNA array analysis in lumbar radiculopathy model has so far focused on the spinal dorsal horn. The molecular changes in the DRG adjacent to the injured nerve root in lumbar radiculopathy remain to be determined. METHODS: Bilateral L5 DRGs were removed from 12 Sprague-Dawley rats on days 2, 7, 14, and 21 after nerve root ligation and on day 7 from 3 rats with sham operation. The aRNAs from the DRGs with nerve root ligation were labeled with Cy5 dye and those from the opposite side DRG (control) were labeled with Cy3 dye, and then hybridized to a 7793-spot Panorama Micro Array. It was considered to be significantly upregulated, when an average expression ratio of Cy5 to Cy3 was 2 or more. Genes upregulated were classified into early phase group (upregulated on day 2), midphase group (upregulated on days 7 and 14), and continuous group (upregulated from day 2 to 21). Seventeen genes were subjected to validation analysis with real-time quantitative PCR. RESULTS: There were 16 upregulated genes in the early phase group, 56 genes in the midphase group, and 17 genes in the continuous group. Functional categorization revealed dominantly upregulated gene categories in each group; transcription/translation in the early phase group, enzyme/metabolism in the midphase group, and structure in the continuous group. Validation analysis of 17 genes demonstrated mean relative expression of 2.0 or more in all but 1 gene in the DRGs with nerve root ligation and none of them in the DRGs with sham operation. CONCLUSION: The genes identified in this study, especially those involved in pain signaling and inflammation, serve as potential targets for molecular-based therapy for lumbar radiculopathy.
The International Journal of Spine Surgery · 2018 · 7 citations · open access
Trends in Nonoperative Treatment Modalities Prior to Cervical Surgery and Impact on Patient-Derived Outcomes: Two-Year Analysis of 1522 Patients From the Prospective Spine Treatment Outcome Study
Abstract<h3>ABSTRACT</h3> <h3>Background:</h3> Effects of nonoperative treatments on surgical outcomes for patients who failed conservative management for cervical spine pathologies remain unknown. The objective is to describe conservative modality use in patients indicated for surgery for degenerative cervical spine conditions and its impact on perioperative outcomes. <h3>Methods:</h3> The current study comprises a retrospective review of a prospective multicenter database. A total of 1522 patients with 1- to 2-level degenerative cervical pathology who were undergoing surgical intervention were included. Outcome measures used were health-related quality-of-life scores, length of hospitalization, estimated blood loss, length of surgery, and return-to-work status at 2 weeks, 6 months, 1 year, and 2 years postoperatively. Patients were grouped by diagnosis (radiculopathy vs. myelopathy), then divided based on epidural injection(s), physical therapy (PT), or opioid use prior to enrollment. Univariate <i>t</i>-tests and χ<sup>2</sup> tests were performed to determine differences between groups and impact on outcomes. <h3>Results:</h3> Among 1319 radiculopathy patients, 25.7% received preoperative epidural injections, 35.3% received PT, and 35.5% received opioids. Radiculopathy patients who received epidurals and PT had higher 1-year postoperative return-to-work rates (<i>P</i> < .05). Radiculopathy patients without preoperative PT had longer hospitalization times, whereas those who received PT had higher 36-Item Short Form Health Survey (SF-36) physical functioning and physical component scores, lower 2-year visual analog scale (VAS) neck/arm pain scores, and higher 2-year return-to-work incidence (<i>P</i> < .05). Of myelopathy patients (n = 203), 14.8% received epidural injections, 25.1% received opioids, and 41.5% received PT. Myelopathy patients with preoperative PT had worse VAS arm pain scores 2 years postoperatively (<i>P</i> < .05). Patients receiving opioids were younger and had greater baseline–2-year Neck Disability Index improvement (<i>P</i> < .05). <h3>Conclusions:</h3> Radiculopathy patients receiving epidurals returned to work after 1 year more frequently. PT was associated with shorter hospitalizations, greater SF-36 bodily pain norm and physical component score improvements, and increased return-to-work rates after 1 and 2 years. No statistically significant nonoperative treatment was associated with return-to-work rate in myelopathy patients. <h3>Clinical Relevance:</h3> These findings suggest certain preoperative conservative treatment modalities are associated with improved outcomes in radiculopathy patients.
Treating Radiculopathy with an Indwelling EpiduralCatheter and Infusion Pump
AbstractBACKGROUND: For the purpose of reducing inflammation causing radiculopathy, lumbar transforaminal and interlaminar epidural injections deliver corticosteroid to the vicinity of the spinal nerve, nerve roots, and intervertebral disc. Although acceptable, the efficacy of transforaminal injections is limited and variable. An indwelling epidural catheter offers the distinct advantages of delivering greater concentrations of corticosteroid directly to the site of pathology, over an extended duration. This extended exposure to corticosteroid may benefit the site of pathology. OBJECTIVE: To evaluate the safety and efficacy of corticosteroid administered through a disposable indwelling epidural catheter and infusion pump to treat pain and dysfunction caused by lumbosacral radiculopathy. STUDY DESIGN: A pilot investigation consisting of a prospective consecutive series of 10 patients, conducted in a specialty hospital. METHODS: An indwelling epidural catheter dispensed corticosteroid into the epidural space at the suspect level of pathology. The catheter was attached to an external, lightweight, spring-pressurized, and disposable reservoir pump holding 8.0 mg dexamethasone diluted with bacteriostatic normal saline to a total volume of 72 ml. After each patient's hospital discharge, the medication was administered into the epidural space at a rate of 1 ml per hour over a 72-hour period. Follow-up at six weeks was achieved in 100% of the patients. OUTCOME MEASURES: The outcome measures, recorded at pre-treatment and six weeks post-treatment were assessed using: the Visual Analog Scale (VAS); MOS 36-Item Short-Form Health Survey (SF-36); Pain Symptoms Survey; Oswestry Disability Index; Beck Inventory; Work History Survey; Work Index; Expectations Met Survey; Activities of Daily Living Form; and the Satisfaction With Treatment Form. RESULTS: There was no patient morbidity or mortality associated with this treatment, and patients, on average, experienced decreased pain levels after treatment. Mean delta VAS improvement was 4.1 (SD = 2.6, R =-9.6 to +1.5). The mean percent improvement was 46.7%. CONCLUSIONS: Safe and effective treatment of lower extremity radiculopathy symptoms may be obtained with this new method.
British Journal of Neurosurgery · 2025 · 0 citations
Effects of revision lumbar microdiscectomy and scarectomy versus scarectomy micro-surgery alone in pain perception: a retrospective pilot study
AbstractAIM: The aim of this study was to assess if patients undergoing redo microdiscectomy surgery, having scarectomy alone, reported having similar levels of pain relief to patients having surgery for recurrent disc. Scar tissue development is inevitable following lumbar surgery. Scar tissue can have a negative impact on patient's reported quality of life, however most surgeons are reluctant to operate primarily to remove this tissue for fear of a CSF leak and reported poor clinical outcomes. However, studies to date have reported only on outcomes following open surgery. Outcomes for microsurgical removal of scar tissue have not been reported. METHODS: We carried out a retrospective cohort study. We reviewed pre-op letters, operative notes and follow-up clinic letters for patients who underwent revision lumbar discectomy for radiculopathy between 2018 and 2022 at a single institution in Dublin. All patients had their pre and post operative level of pain recorded in clinic letters, using the visual analogue score (VAS). RESULTS: Our data suggests that complete resection of scar tissue alone seems to have similar improved VAS scores when compared to those having a revision microdiscectomy. Over 92% of patients in our study had an improvement in pain when undergoing removal of scar tissue. CONCLUSION: Our small cohort study suggests there is improved post-operative pain scores for those patients who underwent scarectomy for recurrence of radiculopathy.
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.
