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Clinical orthopaedics and related research2000; (379 Suppl); S273-S287; doi: 10.1097/00003086-200010001-00037

Evaluation of gene therapy as a treatment for equine traumatic arthritis and osteoarthritis.

Abstract: 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.
Publication Date: 2000-10-20 PubMed ID: 11039781DOI: 10.1097/00003086-200010001-00037Google Scholar: Lookup
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  • Evaluation Study
  • Journal Article

Summary

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The research article explores the evaluation of gene therapy as a potential treatment for osteoarthritis in horses, with potential implications for humans. They found that transferring the gene for an interleukin-1 receptor antagonist through viral methods led to positive outcomes.

Objective of the Study

The primary objective of the study was to investigate the effectiveness of gene therapy as a treatment for trauma-induced arthritis and osteoarthritis in horses. This approach is potentially important as these diseases pose considerable social and economic challenges, and horses are a suitable model due to the similarity of their osteoarthritis to humans’.

  • The researchers were particularly keen on exploring the effects of overexpressing the equine interleukin-1 receptor antagonist gene through adenoviral-mediated gene transfer.

Methodology

Using an established model of equine osteoarthritis, the study pursued the exploration of the therapeutic results that arise from the overexpression of the equine interleukin-1 receptor antagonist gene.

  • This was achieved through adenoviral-mediated gene transfer, a method typically used to deliver genes into a patient’s cells.
  • The researchers carefully monitored various parameters, such as the upregulation of interleukin-1 receptor antagonist protein expression and the improvement in clinical parameters of pain and disease activity.

Findings of the Study

The researchers observed favorable effects from this gene transfer.

  • They found an approximately 28-day upregulation of interleukin-1 receptor antagonist protein expression. An upregulation means an increase in the gene’s activity, leading to more production of the protein it codes for.
  • A significant improvement in clinical parameters of pain and disease activity was noted. The horses with the gene transfer exhibited less pain and disease activity than those without it.
  • The study also flagged beneficial effects on histologic parameters measured from synovial membrane and articular cartilage when compared with nontransduced joints. This indicates improved joint health and function after the gene transfer.

Conclusion and Future Implications

Overall, the results of the study suggest that gene transfer of the interleukin-1 receptor antagonist might be a practical treatment modality for horses suffering from arthritis and osteoarthritis.

  • This form of treatment offers promise in advancing therapeutics for such diseases.
  • The successful results also bode well for potential application in human patients in the future, given the similarity between human and horse osteoarthritis.

Cite This Article

APA
Frisbie DD, McIlwraith CW. (2000). Evaluation of gene therapy as a treatment for equine traumatic arthritis and osteoarthritis. Clin Orthop Relat Res(379 Suppl), S273-S287. https://doi.org/10.1097/00003086-200010001-00037

Publication

ISSN: 0009-921X
NlmUniqueID: 0075674
Country: United States
Language: English
Issue: 379 Suppl
Pages: S273-S287

Researcher Affiliations

Frisbie, D D
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
McIlwraith, C W

    MeSH Terms

    • Animals
    • Arthritis / metabolism
    • Arthritis / pathology
    • Arthritis / therapy
    • Arthritis / veterinary
    • Cartilage, Articular / metabolism
    • Cartilage, Articular / pathology
    • Cells, Cultured
    • Gene Transfer Techniques
    • Genetic Therapy / veterinary
    • Genetic Vectors
    • Horse Diseases / therapy
    • Horses / injuries
    • Humans
    • Interleukin 1 Receptor Antagonist Protein
    • Joints / injuries
    • Osteoarthritis / metabolism
    • Osteoarthritis / pathology
    • Osteoarthritis / therapy
    • Osteoarthritis / veterinary
    • Receptors, Interleukin-1 / antagonists & inhibitors
    • Sialoglycoproteins / genetics
    • Sialoglycoproteins / metabolism
    • Synovial Membrane / metabolism
    • Synovial Membrane / pathology

    Citations

    This article has been cited 9 times.
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    8. Marković L, Vićić I, Lazarević Macanović M, Francuski Andrić J, Kovačević Filipović M, Radaković M. Degenerative Changes in MCP/MTP Joints of Working Horses Without Lameness: Integrating CT-Based Assessment and Synovial Fluid Biomarkers. Animals (Basel) 2025 Nov 24;15(23).
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    9. Thampi P, Seabaugh KA, Pezzanite LM, Chu CR, Phillips JN, Grieger JC, McIlwraith CW, Samulski RJ, Goodrich LR. A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis. Gene Ther 2023 Dec;30(12):792-800.
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