Plasmid growth hormone releasing hormone therapy in healthy and laminitis‐afflicted horses—evaluation and pilot study

Abstract

In vivo electroporation dramatically improves the potency of plasmid-mediated therapies, including in large animal models. Laminitis and arthritis are common and debilitating diseases in the horse, as well as humans. The effects of growth hormone releasing hormone (GHRH) on healthy horses and on horses with laminitis that were followed for 6 months after a single intramuscular injection and electroporation of 2.5 mg of an optimized myogenic GHRH-expressing plasmid were examined. In the first study on six healthy horses, we observed a significant increase in body mass by day 180 compared to baseline (P < 0.003), and an increase in erythrocyte production (hematocrit, red blood cells, hemoglobin, P = 0.03). IGF-I levels were increased by 7% by day 120 (P = 0.02). A pilot study was performed on two horses with chronic laminitis, a vascular condition often associated with arthritis, with two horses with similar clinical disease serving as non-treated controls. Treated horses experienced an increase in weight compared to control horses that received standard care (P = 0.007). By 6 months post-treatment, treated subjects were rated pasture sound. Physical and radiographic evaluation demonstrated significant improvement with reduced inflammation and decreased lameness. These results demonstrate that a plasmid therapy delivered by electroporation can potentially be used to treat chronic conditions in horses, and possibly other very large mammals. While further studies are needed, overall this proof-of-concept work presents encouraging data for studying gene therapeutic treatments for Raynaud's syndrome and arthritis in humans.