title: Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis.
abstract: Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of β2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits β2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging.
authors.affiliation: Division of Nephrology and Hemodialysis, Salvatore Maugeri Foundation, IRCCS Rehabilitation Institute, Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montagna
authors.forename: Benedetta
authors.initials: B
authors.lastname: Cazzulani
authors.forename: Laura
authors.initials: L
authors.lastname: Obici
authors.forename: Carla
authors.initials: C
authors.lastname: Uggetti
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Porcari
authors.forename: Rubina
authors.initials: R
authors.lastname: Ruggiero
authors.forename: P Patrizia
authors.initials: PP
authors.lastname: Mangione
authors.forename: Moreno
authors.initials: M
authors.lastname: Brambilla
authors.forename: Jacopo
authors.initials: J
authors.lastname: Lucchetti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Guiso
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.forename: Monica
authors.initials: M
authors.lastname: Stoppini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villa
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
mesh_terms: D000686:Amyloidosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004318:Doxycycline / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008023:Ligaments, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006435:Renal Dialysis / Q000009:adverse effects*; D012785:Shoulder Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001613:beta 2-Microglobulin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D001613:beta 2-Microglobulin; D004318:Doxycycline