Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses.
Authors: Rahnama Samira, Vathsangam Niveditha, Spence Robert, Medina-Torres Carlos E, Pollitt Christopher C, de Laat Melody A, Bailey Simon R, Sillence Martin N
Journal: PloS one
Summary
# Editorial Summary Endocrinopathic laminitis remains clinically challenging because whilst prolonged hyperinsulinaemia is recognised as the causative mechanism, the precise pathological pathway—and therefore how to interrupt it therapeutically—remains poorly understood. Researchers hypothesised that excessive insulin concentrations might activate insulin-like growth factor-1 receptors (IGF-1R) in lamellar tissue, driving pathological cell proliferation and structural failure; to test this, they administered an equine-adapted anti-IGF-1R monoclonal antibody (mAb11) to one forelimb of Standardbred horses via retrograde infusion whilst inducing experimental hyperinsulinaemic laminitis over 48 hours using a euglycaemic clamp technique, with saline-treated and insulin-only controls. All insulin-infused horses developed clinical and radiographic laminitis within 30 hours, yet the antibody-treated group showed significantly less distal phalanx sinking and milder histopathological changes, particularly reduced elongation of secondary epidermal lamellar tips. Although mAb11 did not prevent laminitis entirely, these results provide evidence that IGF-1R signalling contributes meaningfully to insulin-induced lamellar damage and suggest targeting this pathway may offer therapeutic benefit for endocrinopathic cases. For practitioners managing insulin-dysregulated horses, this research signals a potential future treatment avenue, though further work is needed to optimise dosing, delivery methods, and long-term safety profiles before clinical translation.
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Practical Takeaways
- •IGF-1 receptor inhibition shows promise as a therapeutic target for endocrinopathic laminitis, though blocking this pathway alone does not prevent the disease entirely
- •Current findings suggest combination therapy may be needed alongside IGF-1R antagonism to fully prevent hyperinsulinaemia-induced laminitis
- •This research identifies a potential new drug class for treating insulin-associated laminitis in horses with metabolic disease, but further development is required before clinical application
Key Findings
- •All insulin-treated horses developed laminitis within 30 hours regardless of antibody treatment, confirming hyperinsulinaemia's laminitic effect
- •mAb11-treated horses showed significantly less distal phalanx sinking compared to positive-control (P < 0.05)
- •Anti-IGF-1R antibody treatment reduced histological severity with markedly less elongation of secondary epidermal lamellae tips (P < 0.05)
- •IGF-1 receptor appears to play a role in insulin-induced laminitis pathogenesis but does not account for all mechanisms of hyperinsulinaemic injury