title: Treatment for experimental autoimmune neuritis with clodronate (Bonefos).
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.
authors.affiliation: Department of Neurology, Sheba Medical Center, 52621, Tel Hashomer, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Katzav
authors.forename: Hofit
authors.initials: H
authors.lastname: Bina
authors.forename: Ramona
authors.initials: R
authors.lastname: Aronovich
authors.forename: Joab
authors.initials: J
authors.lastname: Chapman
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D015415:Biomarkers / Q000378:metabolism; D004002:Clodronic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D003711:Demyelinating Diseases / Q000188:drug therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018996:Myelin P2 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013577:Syndrome
chemical_list: D015415:Biomarkers; D018996:Myelin P2 Protein; D004002:Clodronic Acid; D020780:Matrix Metalloproteinase 9