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: Giovanni Montagna, Benedetta Cazzulani, Laura Obici, Carla Uggetti, Sofia Giorgetti, Riccardo Porcari, Rubina Ruggiero, P Patrizia Mangione, Moreno Brambilla, Jacopo Lucchetti, Giovanna Guiso, Marco Gobbi, Giampaolo Merlini, Mario Salmona, Monica Stoppini, Giuseppe Villa, Vittorio Bellotti
• Journal: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis (Amyloid) Vol. 20 Issue 3 Pg. 173-8 (Sep 2013) ISSN: 1744-2818 [Electronic] England
• PMID: 23734692 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• beta 2-Microglobulin
• Doxycycline

Topics

• Amyloidosis (drug therapy, etiology, metabolism, pathology)
• Arthralgia (drug therapy, etiology, metabolism, pathology)
• Bone and Bones (drug effects, metabolism, pathology)
• Doxycycline (pharmacokinetics, therapeutic use)
• Humans
• Ligaments, Articular (drug effects, metabolism, pathology)
• Male
• Middle Aged
• Pain, Intractable (drug therapy, etiology, metabolism, pathology)
• Plaque, Amyloid (etiology, metabolism, pathology)
• Renal Dialysis (adverse effects)
• Shoulder Joint (drug effects, metabolism, pathology)
• beta 2-Microglobulin (antagonists & inhibitors, chemistry, metabolism)