Pilot Study of an Alpha-2-Macroglobulin-Enriched Plasma-Derived Orthobiologic Preparation in Sport Horses with Chronic Degenerative Joint Disease

Chronic joint disease is a major cause of lameness and reduced performance in sport horses and is characterized by persistent synovial inflammation and protease-mediated matrix degradation. This exploratory prospective pilot study investigated clinical outcomes and synovial biomarker changes following intra-articular administration of an α-2-macroglobulin plasma-derived preparation. Twenty client-owned sport horses were observed in the treatment group (n = 10) or a comparison group (n = 10) and monitored for up to 180 days under field conditions. Clinical outcomes were assessed longitudinally, while synovial fluid was analyzed at baseline and 30 days post-treatment only in treated horses. Mixed-effects analysis showed significant group × time interactions for American Association of Equine Practitioners (AAEP) lameness score, flexion test response, and joint effusion. Treated horses showed early and sustained improvement in clinical scores, whereas minimal changes were observed in the comparison group. At 30 days, treated horses exhibited consistent within-subject reductions in synovial total protein, total nucleated cell count, polynuclear cell percentage, pro-inflammatory cytokines (PGE2, TNF-α, IL-6, IL-1β), matrix metalloproteinases (MMP-9, MMP-13), sulphated glycosaminoglycans, and neurogenic mediators (NGF, Substance P). These findings indicate a coherent pattern of clinical improvement associated with parallel changes in synovial biomarkers in treated horses. However, as longitudinal biomarker data were not collected in the comparison group, these observations should be interpreted as exploratory and do not establish causality. The observed findings support the rationale for further investigation of protease-targeted approaches in equine joint disease.