TY - JOUR
T1 - Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis
AU - Montagna, Giovanni
AU - Cazzulani, Benedetta
AU - Obici, Laura
AU - Uggetti, Carla
AU - Giorgetti, Sofia
AU - Porcari, Riccardo
AU - Ruggiero, Rubina
AU - Patrizia Mangione, P.
AU - Brambilla, Moreno
AU - Lucchetti, Jacopo
AU - Guiso, Giovanna
AU - Gobbi, Marco
AU - Merlini, Giampaolo
AU - Salmona, Mario
AU - Stoppini, Monica
AU - Villa, Giuseppe
AU - Bellotti, Vittorio
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - β2-Microglobulin
KW - Amyloid fibrils
KW - Inhibition of fibrillogenesis
KW - Long-term dialysis
KW - Tetracyclines
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UR - http://www.scopus.com/inward/citedby.url?scp=84882962397&partnerID=8YFLogxK
U2 - 10.3109/13506129.2013.803463
DO - 10.3109/13506129.2013.803463
M3 - Article
C2 - 23734692
AN - SCOPUS:84882962397
VL - 20
SP - 173
EP - 178
JO - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
SN - 1350-6129
IS - 3
ER -