Targeted interleukin-10 plasmid DNA therapy in the treatment of osteoarthritis: Toxicology and pain efficacy assessments
| Autor: | Suzanne M. Green-Fulgham, Megan Fry, Robert Landry, Collins Stephen, Raymond A. Chavez, David K. Glover, John Forsayeth, Jonathan D. Coulson, Jayson M. Rieger, Linda R. Watkins |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Immunology Pain Osteoarthritis Targeted therapy Proinflammatory cytokine Toxicology 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Dogs In vivo medicine Animals Endocrine and Autonomic Systems business.industry Chronic pain Genetic Therapy Osteoarthritis Knee medicine.disease Interleukin-10 Clinical trial Interleukin 10 030104 developmental biology Cytokine business 030217 neurology & neurosurgery Plasmids |
| Zdroj: | Brain, behavior, and immunity. 90 |
| ISSN: | 1090-2139 |
| Popis: | Osteoarthritis results in chronic pain and loss of function. Proinflammatory cytokines create both osteoarthritis pathology and pain. Current treatments are poorly effective, have significant side effects, and have not targeted the cytokines central to osteoarthritis development and maintenance. Interleukin-10 is an anti-inflammatory cytokine that potently and broadly suppresses proinflammatory cytokine activity. However, interleukin-10 protein has a short half-life in vivo and poor joint permeability. For sustained IL-10 activity, we developed a plasmid DNA-based therapy that expresses a long-acting human interleukin-10 variant (hIL-10var). Here, we describe the 6-month GLP toxicology study of this therapy. Intra-articular injections of hIL-10var pDNA into canine stifle joints up to 1.5 mg bilaterally were well-tolerated and without pathologic findings. This represents the first long-term toxicologic assessment of intra-articular pDNA therapy. We also report results of a small double-blind, placebo-controlled study of the effect of intra-articular hIL-10var pDNA on pain measures in companion (pet) dogs with naturally occurring osteoarthritis. This human IL-10-based targeted therapy reduced pain measures in the dogs, based on veterinary and owner ratings, without any adverse findings. These results with hIL-10var pDNA therapy, well-tolerated and without toxicologic effects, establish the basis for clinical trials of a new class of safe and effective therapies for OA. |
| Databáze: | OpenAIRE |
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