Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)173-178
Number of pages6
JournalAmyloid
Volume20
Issue number3
DOIs
Publication statusPublished - Sep 2013

Keywords

  • β2-Microglobulin
  • Amyloid fibrils
  • Inhibition of fibrillogenesis
  • Long-term dialysis
  • Tetracyclines

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis'. Together they form a unique fingerprint.

  • Cite this

    Montagna, G., Cazzulani, B., Obici, L., Uggetti, C., Giorgetti, S., Porcari, R., Ruggiero, R., Patrizia Mangione, P., Brambilla, M., Lucchetti, J., Guiso, G., Gobbi, M., Merlini, G., Salmona, M., Stoppini, M., Villa, G., & Bellotti, V. (2013). Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis. Amyloid, 20(3), 173-178. https://doi.org/10.3109/13506129.2013.803463