Peer-reviewed veterinary case report
Anti-IGF-1 receptor antibody tested for insulin-related laminitis
By Rahnama, Samira et al.·Published in PloS one·2020·Biology and Environmental Sciences School, Australia·View original on PubMed →
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Original publication title: Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses.
- Species:
- horse
Plain-English summary
A group of Standardbred horses developed laminitis, a painful hoof condition, after being given high levels of insulin for 48 hours. While all the insulin-treated horses showed signs of laminitis, those that also received a special antibody treatment (mAb11) had less severe symptoms and less damage to their hooves compared to those that only received insulin. The antibody seemed to help reduce the sinking of the hoof bone and the extent of tissue damage. This study suggests that mAb11 could be a promising treatment for laminitis caused by insulin issues in horses, but more research is needed.
People also search for: horse laminitis treatment · insulin laminitis in horses · Standardbred horse hoof problems
Abstract
Currently, there are no registered veterinary drugs for the treatment of endocrinopathic equine laminitis, and although this form of the disease is known to be caused by prolonged hyperinsulinaemia, the mechanism of insulin toxicity is unclear. One possibility is that high concentrations of insulin activate IGF-1 receptors (IGF-1R) in lamellar tissue, leading to uncontrolled cell proliferation and epidermal lamellar dysregulation. An equinized version of a human anti-IGF-1R therapeutic monoclonal antibody (mAb11) was generated to test this theory, using a modification of the prolonged euglycaemic-hyperinsulinaemic clamp technique. Healthy Standardbred horses were infused for 48 h with 0.9% saline (negative-control, n = 6), a combination of insulin (4.5 mIU/kgBW/min) and a variable infusion of 50% glucose to maintain euglycaemia (positive-control, n = 6), or insulin and glucose, preceded by a low dose of mAb11 (20 mg), designed to treat one foot only and delivered by retrograde infusion into one forelimb (mAb-treated, n = 7). Maximum insulin concentrations were 502 ± 54.4 and 435 ± 30.4 μIU/mL in the positive-control and mAb11-treated groups, respectively (P = 0.33). While the control group remained healthy, all the insulin-treated horses developed laminitis within 30 h, as judged by clinical examination, foot radiographs and histological analysis. Some effects of insulin were not attenuated by the antibody, however, relative to the positive-control group, horses treated with mAb11 showed less sinking of the distal phalanx (P < 0.05) and milder histological changes, with markedly less elongation at the tips of the secondary epidermal lamellae (P < 0.05). These differences were apparent in both front feet and were statistically significant when the values for both feet were combined. The results confirm that IGF-1R may have a role in insulin-induced laminitis and suggest that mAb11 warrants further research as a potential agent to prevent or treat the disease.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/32991593/