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Treatment for experimental autoimmune neuritis with clodronate (Bonefos)

  • Treatment of Autoimmunity
  • Published:
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Abstract

Experimental autoimmune neuritis (EAN) serves as an animal model for human Gullain–Barre syndrome (GBS), an autoimmune disease causing demyelination and inflammation of peripheral nerves. Macrophages, which play a major role in this autoimmune inflammatory process, can be selectively targeted by high doses of bisphophonates. The goal of this study was to examine the effect of the bisphosphonate, clodronate, on the severity of the EAN model. EAN was induced in female adult rats by immunization with bovine peripheral myelin. A number of treatment protocols with clodronate were used based on the common dosage regimen of 20 mg/kg in humans starting with the appearance of clinical signs on day 10 post-immunization. The clinical parameters measured included a clinical score, a motor performance test performed on a Rotarod and body weight. The expression of the matrix metaloprotease (MMP-9) in the sciatic nerves was measured as a marker of inflammatory macrophages. Treatment with clodronate, 20 mg/kg daily and 40 mg/kg every 2 days, significantly reduced the disease severity (a 75 % decrease in severity, p < 0.01 by ANOVA) as measured by the clinical score compared to controls. Performance on the Rotarod test and body weight confirmed the clinical score findings. MMP-9 expression levels were significantly lower in the sciatic nerves of clodronate-treated rats. The present findings support the efficiency of clodronate in inflammatory diseases of the peripheral nervous system. The mechanism of action includes inhibition of inflammatory macrophages. The results suggest the use of bisphosphonates be considered in humans with GBS.

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Authors and Affiliations

  1. Department of Neurology and Joseph Sagol Neuroscience Center, Sheba Medical Center, 52621, Tel Hashomer, Israel

    Aviva Katzav & Joab Chapman

  2. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Hofit Bina, Ramona Aronovich & Joab Chapman

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  1. Aviva Katzav
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  2. Hofit Bina
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  3. Ramona Aronovich
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  4. Joab Chapman
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Correspondence to Joab Chapman.

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Katzav, A., Bina, H., Aronovich, R. et al. Treatment for experimental autoimmune neuritis with clodronate (Bonefos). Immunol Res 56, 334–340 (2013). https://doi.org/10.1007/s12026-013-8406-y

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  • DOI: https://doi.org/10.1007/s12026-013-8406-y

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