Evaluation of gene therapy as a treatment for equine traumatic arthritis and osteoarthritis.
Joint disease in horses and in humans is a significant social and economic problem and continued research and improvements in therapeutics are needed. Because horses have naturally occurring osteoarthritis that is similar to that of humans, the horse was chosen as a species to investigate gene transfer as a potential therapeutic modality for the treatment of osteoarthritis. Using an established model of equine osteoarthritis, the therapeutic effects resulting from overexpression the equine interleukin-1 receptor antagonist gene sequence through adenoviral mediated gene transfer was investigated. The results of the current study showed intraarticular expression of interleukin-1 receptor antagonist to have favorable effects such as an approximately 28 day upregulation of interleukin-1 receptor antagonist protein expression, significant improvement in clinical parameters of pain and disease activity, and beneficial effects in histologic parameters measured from synovial membrane and articular cartilage when compared with nontransduced joints. Based on the significant improvements seen in this work gene transfer of interleukin-1 receptor antagonist is a practical treatment modality for the equine patient and also offers future promise for human patients.
Frisbie
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DD
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
McIlwraith
C W
CW
D000818:Animals; D001168:Arthritis / Q000378:metabolism / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000662:veterinary*; D005822:Genetic Vectors; D006734:Horse Diseases / Q000628:therapy*; D006736:Horses / Q000293:injuries; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007596:Joints / Q000293:injuries; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000628:therapy / Q000662:veterinary; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins