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This gap reflects the inconsistent relationship between degeneration and pain, compounded by heterogeneous patient populations, insufficient phenotyping, and inadequate selection of truly discogenic LBP patients in current trials. Emerging evidence indicates that IDD and LBP comprise distinct biological endotypes, requiring matched therapeutic strategies, or \u201ctheratypes\u201d, rather than uniform approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this narrative review, we critically examined the current evidence on biologic therapies for IDD, focusing on the translational gap between preclinical success and clinical outcomes. We analyzed key methodological and biological limitations, including patient heterogeneity, pain misclassification, inadequate phenotyping, and suboptimal trial design. Additionally, we reviewed emerging concepts such as disease phenotyping, mechanism\u2010based patient selection, and stage\u2010adapted therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Multiple barriers hinder clinical translation of biologic therapies for IDD, including incomplete understanding of disc biology, limited intrinsic regenerative capacity, and a hostile tissue microenvironment. Preclinical models frequently fail to replicate the complexity of human pathology and pain, while clinical trials rely heavily on subjective outcomes and are often confounded by strong placebo effects. Furthermore, regulatory, logistical, and economic challenges limit widespread clinical adoption. Progress in the field will require a shift toward precision medicine approaches to align therapies with specific endotypes, pain phenotypes, and stages of IDD. Greater standardization, transparency, and community\u2010wide reporting practices are also essential to improve reproducibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Advancing biologic therapies for IDD will depend on the development of more precise and biologically informed clinical strategies. Improved patient stratification, better alignment between therapeutic mechanisms and disease biology, and the adoption of standardized and clinically meaningful outcome measures are critical. Despite recent progress, key pathophysiological mechanisms remain poorly understood, underscoring the need for rigorous and multidisciplinary research efforts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70187","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T05:44:30Z","timestamp":1783143870000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lost in Translation: Why Biologic Therapies for Intervertebral Disc Degeneration and Low Back Pain Have Not Reached the Clinic (Yet)"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2424-1274","authenticated-orcid":false,"given":"Luca","family":"Ambrosio","sequence":"first","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome 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