Abstract
Osteoarthritis (OA) treatments presently rely on analgesics, which manage pain but fail to restore imbalances between catabolic and anabolic processes that underlie OA pathogenesis. Recently, biologic (biotherapeutic) drugs, which alter the activity of catabolic agents such as nitric oxide and inflammatory cytokines in ways, allowing tissue regeneration, were evaluated for efficacy in OA treatment. These studies failed to demonstrate dramatic abatement of OA symptoms by these drugs, but suggested strategies by which biologic agents might be used to treat OA. The present review summarizes current understanding of OA pathogenesis and evolving treatments. Preliminary evaluations of a novel biotherapeutic strategy are presented here. Twenty OA patients receiving sour topical cherry seed extract (SCE), an inducer of heme oxygenase-1 (HO-1), a major physiological protectant against oxidative stress exhibited significantly decreased joint pain and activation of CD4+ T cells expressing inflammatory cytokines (p < 0.05), significantly decreased peripheral blood C-reactive protein (CRP), and increased leukocyte HO-1 (p < 0.05) in comparison with ten placebo-treated patients. SCE inhibits joint-damaging inflammatory mediator production. This agent therefore meets the main criterion for classification as a “biotherapeutic,” or “biologic” agent. The negligible toxicity and low cost of such materials make them promising contributors to OA treatment, sustainable within resource limitations of a wide range of patients.
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Acknowledgments
The authors extend sincere thanks to all OA patients who participated in this research. We are grateful to Mr. Basel Ibrahim for his technical assistance, and to Stephanie C. Fox, J.D. for her editing.
Author contributions
The author contributions may be summarized as follows: Dr. Fadia Mahmoud made the concept and design of the study, data acquisition and data analysis. Dr. David Haines identified the chemical composition of emulsifying material required to stabilize sour cherry seed components of differing solubility in a carbamide vehicle. Drs. Mahmoud and Haines contributed equally to data interpretation and written presentation of the results. Overall supervision of patient care and monitoring was provided by Prof. Adel Al-Awadhi M.D.
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The authors declare no competing interests.
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Mahmoud, F.F., Al-Awadhi, A.M. & Haines, D.D. Amelioration of human osteoarthritis symptoms with topical ‘biotherapeutics’: a phase I human trial. Cell Stress and Chaperones 20, 267–276 (2015). https://doi.org/10.1007/s12192-014-0553-0
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DOI: https://doi.org/10.1007/s12192-014-0553-0