Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial.
Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial.
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perhexiline在治疗纤维肿瘤的骨质体progressecriva：一项开放标记的临床试验中。
DOI：
10.1186/1750-1172-8-163
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发表时间：
2013-10-16
影响因子：
3.7
通讯作者：
Ishiguro N
中科院分区：
文献类型：
--
作者：
Kitoh H;Achiwa M;Kaneko H;Mishima K;Matsushita M;Kadono I;Horowitz JD;Sallustio BC;Ohno K;Ishiguro N
目前，对于进行性骨化纤维发育不良(FOP)患者，尚无有效的药物治疗方案来预防异位骨的形成。通过药物重新定位策略，我们证实了马来酸培己胺(PEX)潜在地改善了模型细胞和小鼠的异位骨化。在这里，我们进行了一项前瞻性研究，以评估Pex治疗FOP患者的有效性和安全性。在这项开放标签单中心研究中，FOP患者接受了总共12个月的Pex治疗，并在停药后连续12个月进行了随访。定期通过体格检查和血液检查评估治疗的安全性。Pex预防异位骨化的效果是通过突发事件、血清骨标记物的测量和三维计算机断层扫描(3D-CT)图像计算的总骨体积的变化来评估的。入选患者5例，平均年龄23.4岁。在每个人服用Pex的安全剂量范围内，在用药阶段没有出现药物引起的不良反应。三名患者在研究期间没有表现出强烈的炎症反应，而两名患者在药物治疗阶段出现了髋关节周围的急性发作，没有创伤的证据。此外，其中一人在停药阶段逐渐无法张开嘴。血清碱性磷酸酶(ALP)和骨特异性碱性磷酸酶(BAP)水平随发病时间的延长而显著升高。体积3D-CT分析显示，在两年的研究期间，病例2(378 cm~3)和病例3(833 cm~3)的总骨体积显著增加。我们不能证明口服Pex预防FOP异位骨化的有效性。血清ALP和BAP水平有望成为监测异位骨化发展和治疗效果的生物标志物。在即将进行的FOP临床试验中，通过全身CT扫描量化总骨体积的变化可能是一种可靠的疾病进展评估工具。
Currently, there are no effective medical treatment options to prevent the formation of heterotopic bones in fibrodysplasia ossificans progressiva (FOP). By the drug repositioning strategy, we confirmed that perhexiline maleate (Pex) potentially ameliorates heterotopic ossification in model cells and mice. Here, we conducted a prospective study to assess the efficacy and safety of Pex in the treatment of FOP patients. FOP patients in this open-label single-center study were treated with Pex for a total of 12 months, and followed up for 12 consecutive months after medication discontinuation. The safety of the treatment was assessed regularly by physical and blood examinations. The efficacy of Pex for preventing heterotopic ossifications was evaluated by the presence of flare-ups, measurements of serum bone markers, and changes in the total bone volume calculated by the three-dimensional computed tomography (3D-CT) images. Five patients with an average age of 23.4 years were enrolled. Within safe doses of Pex administration in each individual, there were no drug-induced adverse effects during the medication phase. Three patients showed no intense inflammatory reactions during the study period, while two patients had acute flare-ups around the hip joint without evidence of trauma during the medication phase. In addition, one of them became progressively incapable of opening her mouth over the discontinuation phase. Serum levels of alkaline phosphatase (ALP) and bone specific ALP (BAP) were significantly and synchronously increased with the occurrence of flare-ups. Volumetric 3D-CT analysis demonstrated a significant increase in the total bone volume of Case 2 (378 cm3) and Case 3 (833 cm3) during the two-year study period. We could not prove the efficacy of oral Pex administration in the prevention of heterotopic ossifications in FOP. Serum levels of ALP and BAP appear to be promising biomarkers for monitoring the development of ectopic ossifications and efficacy of the therapy. Quantification of change in the total bone volume by whole body CT scanning could be a reliable evaluation tool for disease progression in forthcoming clinical trials of FOP.
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影响因子：
3.7
作者：
Pignolo RJ;Shore EM;Kaplan FS
通讯作者：
Kaplan FS
DOI：
10.1016/j.berh.2007.11.007
发表时间：
2008-03-01
影响因子：
5.2
作者：
Kaplan, Frederick S.;Le Merrer, Martine;Groppe, Jay
通讯作者：
Groppe, Jay
影响因子：
30.8
作者：
Shore, EM;Xu, MQ;Kaplan, FS
通讯作者：
Kaplan, FS
影响因子：
14.8
作者：
Yui, Paul B.;Hong, Charles C.;Peterson, Randall T.
通讯作者：
Peterson, Randall T.
影响因子：
4.8
作者：
Fukuda, Toru;Kohda, Masakazu;Katagiri, Takenobu
通讯作者：
Katagiri, Takenobu