ArticleEuropean spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society2025
IMID-284: a potent pyruvate kinase M2 inhibitor with dual anti-inflammatory and analgesic effects in intervertebral disc disease.
Article in European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The trial behind it
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Who cites it
1 citing paper in PubMed.
- Proteolytic enzyme models as tunable preclinical platforms for investigating intervertebral disc degeneration.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
7 authors.
Funding
Abstract
purposeIntervertebral disc degeneration (IVDD) is a major contributor to lower back pain and disability, driven by alterations in extracellular matrix (ECM) remodelling and inflammation following chondroptosis. While the relationship between IVDD and ECM biochemical changes is well-established, the specific role of pyruvate kinase M2 (PKM2) in this process remains unexplored. This study aimed to investigate the involvement of PKM2 in a Chondroitinase ABC (ChABC)-induced model of IVDD.
methodsWe administered three different dosages of ChABC (0.0001U, 0.00025U, and 0.0005U) in the coccygeal disc. Subsequently, the model was validated through behavioural tests (tail flick and von Frey). Additionally, a comprehensive morphological evaluation of the disc was assessed using H&E, MT, and SO-FG staining. Also, various IHC markers like Collagen-I, II, Aggrecan, and SOX-9 expressions were analyzed.
resultsAdministration of a 0.00025U dose of ChABC at day 28 led to a significant upregulation of PKM2, TSK, IL-1β, and cellular hypertrophy, all hallmarks of IVDD. The onset of IVDD was associated with a decrease in collagen-II, Aggrecan, and markers of chondrogenesis, contributing to increased pain, inflammation, and tissue disorganization. Notably, selective inhibition of PKM2 using IMID-284 resulted in reduced pain and inflammation, alongside a protective effect on cartilage, suggesting that PKM2 plays a pivotal role in IVDD pathophysiology.
conclusionThese findings indicate that PKM2 inhibition may represent a promising therapeutic strategy for mitigating the biochemical and structural changes underlying disc degeneration. Overall, the study provides new insights into how PKM2 inhibition could arrest the progression of IVDD, pain, and inflammation.
Indexed as
Identifiers
40478253What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.