Division of Nephrology and Hemodialysis, Salvatore Maugeri Foundation, IRCCS Rehabilitation Institute, Pavia, Italy.
Amyloid. 2013 Sep;20(3):173-8. doi: 10.3109/13506129.2013.803463. Epub 2013 Jun 4.
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.
多西环素可抑制体外淀粉样蛋白的形成，其治疗效果正在临床试验中评估，用于治疗包括朊病毒病、阿尔茨海默病和转甲状腺素淀粉样变性病等不同蛋白质构象疾病。在慢性血液透析患者中，β2-微球蛋白持续高浓度会导致一种淀粉样变性（透析相关淀粉样变性，DRA），主要发生在骨骼和韧带部位。由于多西环素可抑制β2-微球蛋白纤维形成，并在骨骼中蓄积，因此 DRA 是一种理想的淀粉样变性形式，多西环素可能在淀粉样沉积物部位达到治疗浓度。3 名长期透析且因 DRA 导致严重关节损伤和无法控制疼痛的患者接受了每天 100mg 的多西环素治疗。对治疗的药代动力学和安全性进行了检测。药物的血药浓度在一周后达到平台期（1.1-2.3μg/ml）。2 名患者耐受治疗 1 年，而 1 名患者因轻度食管炎在 5 个月后暂停治疗。治疗与关节疼痛的显著减轻相关，并且在所有患者中，被动和主动运动都有显著且可测量的改善，尽管磁共振成像测量的淀粉样沉积物没有变化。
