Plasmid growth hormone releasing hormone therapy in healthy and laminitis-afflicted horses-evaluation and pilot study.

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.