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A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated.

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Presentation on theme: "A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated."— Presentation transcript:

1 A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain. By Duncan X Lascelles, David Knazovicky, Beth Case, Mila Freire, John F Innes, Alexander C Drew and David P Gearing

2  Alternative to non-steroidal anti-inflammatory drugs (NSAIDs).  Pain relief from osteoarthritis and degenerative joint disease. Introduction http://7-themes.com/6797612-happy-dog-wallpaper.html

3  Development of nervous system.  pro-nociceptor  Binds to NGF-specific tyrosine kinase receptor TrkA  High NGF associated with chronic pain (Shelton et al., 2005) Nerve Growth Factor

4  Remove free NGF  Anti-NGF antibodies inhibit NGF function  Reduces hyperalgesia in osteoarthritic patients. (Hefti et al., 2006)  Canine-specific anti-NGF maB NV-01 (Gearing et al., 2013) NGF as a therapeutic target http://www.mdanderson.org/education-and-research/departments-programs-and-labs/labs/mcbride- laboratory/recombinant-monoclonal-antibody-production/antibody.png

5  “A single treatment of NV-01 will decrease pain and improve mobility in dogs with DJD-associated pain for 4 weeks, as measured by owner-completed clinical metrology instruments (CMIs) and objectively measured activity.” Study hypothesis http://petemergencymelbourne.com.au/wp-content/uploads/2012/07/iStock_000012697467Small.jpg

6  Canine brief pain inventory pain interference score (CBPI PIS)  Canine brief pain inventory pain severity score (CBPI PSS)  Canine brief pain inventory success/failure (CBPI SF)  Client specific outcome measure (CSOM)  Liverpool osteoarthritis in dogs (LOAD)  Quality of life score (QoL)  Activity monitoring Study design

7  Treatment group improved significantly over time.  Placebo group did not improve significantly over time. Results https://c1.staticflickr.com/3/2574/4031512294_8e2a25fd17.jpg

8 Activity Figure 1. Graph of mean change (week 4 minus baseline) in activity each hour. NV- 01 treated dogs= dotted line. Placebo treated dogs= solid line. http://strideaway.com/wp-content/themes/strideaway/_images/common/footerRunningDog.png

9 LOAD scores Figure 2. Change in LOAD scores from baseline over time. a) dogs treated with 200 mcg/kg IV NV-01. b) dogs treated with IV saline placebo.

10  Long half life  Low toxicity  Easy to administer  High specificity and efficiency Potential of NV-01 http://drplechner.com/wp-content/uploads/2014/07/needle.jpg

11  Canine quantitative sensory testing -to evaluate sensory function changes  Human anti-NGF trials saw side effects -1% rapidly progressing osteoarthritis (Bannwarth & Kostine, 2014)  Test larger cohort of dogs Future study http://bristol-chiropractor.com/wp-content/uploads/2014/04/joint-pain.jpg

12  Safe and easy management of chronic pain  Other species potential (Davis & Donnelly, 1968)  Further research required Conclusion https://www.friskies.com/Content/images/headers/cat_wet.png

13  Bannwarth, B., & Kostine, M. (2014). Targeting nerve growth factor (NGF) for pain management: what does the future hold for NGF antagonists? Drugs, 74(6), 619-626.  Davis, L. E., & Donnelly, E. J. (1968). Analgesic drugs in the cat. Journal of the American Veterinary Medical Association, 153(9), 1161.  Gearing, D. P., Virtue, E. R., Gearing, R. P., & Drew, A. C. (2013). A fully caninised anti-NGF monoclonal antibody for pain relief in dogs. BMC veterinary research, 9(1), 226.  Hefti, F. F., Rosenthal, A., Walicke, P. A., Wyatt, S., Vergara, G., Shelton, D. L., & Davies, A. M. (2006). Novel class of pain drugs based on antagonism of NGF. Trends in pharmacological sciences, 27(2), 85-91.  Innes, J. F., Clayton, J., & Lascelles, B. D. X. (2010). Review of the safety and efficacy of long-term NSAID use in the treatment of canine osteoarthritis. The Veterinary Record, 166(8), 226.  Shelton, D. L., Zeller, J., Ho, W. H., Pons, J., & Rosenthal, A. (2005). Nerve growth factor mediates hyperalgesia and cachexia in auto-immune arthritis. Pain, 116(1), 8-16. References


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