So, I hoped that the tetracyclines, presumably as metallo-proteinase inhibitors here, would turn out to have some value in treating patients with OA as well. They don’t.5 At least in this study, under these circumstances, for 24 weeks, twice-daily doxycycline was no better than placebo at relieving symptoms of OA. Adverse effects were considered to offer an unfavorable risk–benefit ratio. Disappointing. It’s hard to contemplate trying higher doses or longer duration of treatment, but maybe they could be used earlier in disease, maybe preventively or prophylactically, insofar as possible, or maybe another metallo-proteinase inhibitor will work.
May You Have a Long Life and Prosper, Progranulin
Progranulin (PGRN), an autocrine growth factor with cytokine-like properties, binds to tumor necrosis factor (TNF) receptors and moderates the action of TNF- in experimental arthritis. It thus has promising therapeutic potential. These elegant experiments found that PGRN bound directly to TNF- receptors, it antagonized TNF- actions, PGRN deficient mice had more severe collagen-induced arthritis than controls, recombinant PGRN reversed disease, and a protein containing 3 PGRN fragment, Atsttrin, was antiarthritic in mouse models and blocked TNF--related intracellular signaling.6,7 The authors’ cautious final statement was “the identification of PGRN and the PGRN-derived protein, ATSTTRIN, as antagonists of TNFR may lead to innovative therapeutics for various pathologies and conditions, such as rheumatoid arthritis.” That would be nice indeed.
Dr. Panush is professor of medicine, Division of Rheumatology, at the Keck School of Medicine, University of Southern California, in Los Angeles.
References
- Crosby V, Wilcock A. End-of-life care in rheumatology. Rheumatol. 2011;50:1187-1188.
- Skinner M, Cathcart ES, Mills JA, Pinals RS. Tetracycline in the treatment of rheumatoid arthritis. A double-blind controlled study. Arthritis Rheum. 1971;14: 727-732.
- O’Dell JR, Haire CE, P almer W, et al. Treatment of early rheumatoid arthritis with minocycline or placebo. Results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 1997;40: 842-848.
- Yu LP Jr, Smith GN Jr, Brandt KD, et al. Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis Rheum. 1992;35:1150–1159.
- Snijders GF, van den Ende CHM, van Riel PLCM, et al. The effects of doxycycline on reducing symptoms in knee osteoarthritis: Results from a triple-blinded randomized controlled trial. Ann Rheum Dis. 2011;70: 1191-1196.
- Tang W, Lu Y, Tian GY, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011;332: 478-484.
- Wu H, Siegel RM. Progranulin resolves inflammation. Science. 2011; 332:427-428.
