Research Article

结合日本HGF基因治疗严重肢体缺血的临床资料分析

卷 20, 期 1, 2020

页: [25 - 35] 页: 11

弟呕挨: 10.2174/1566523220666200516171447

价格: $65

摘要

目的: 利用编码肝细胞生长因子(HGF)的裸质粒DNA对日本临床试验数据进行综合分析,目的是证明肌内HGF基因治疗严重肢体缺血(CLI)患者的安全性和有效性。 方法: 在大阪大学的单中心公开试验中,对22例CLI患者进行HGF基因转移;39名患者参与一项随机、安慰剂对照、多中心III期试验,10名患者参与一项多中心公开试验;6例CLI患者在多中心开放试验中使用2或3例肌肉注射2或4毫克裸HGF质粒。在初次注射后12周,以视觉模拟评分法(VAS)评估静息疼痛和创面愈合情况。77例患者中有7例(9.09%)因基因转移引起严重不良事件。与接受VEGF治疗的患者相比,只有1例患者出现外周水肿(1.30%)。基因移植后12周,HGF基因治疗组VAS和缺血性溃疡大小综合评价较安慰剂组有显著改善(P=0.020)。 结果: 长期分析显示HGF基因治疗组缺血性溃疡的大小持续下降。此外,与安慰剂组相比,HGF基因治疗组在基线时VAS评分超过50mm(共有27例患者)有提高VAS评分的趋势(P=0.059),但并不显著。结论:肌肉注射裸HGF质粒可改善无血管内治疗或旁路移植手术等替代治疗的CLI患者静息疼痛,并可显著降低缺血性溃疡的大小。最近,一种HGF基因治疗产品CollategeneTM在日本上市,并获得有条件和有时限的批准,用于治疗CLI患者的缺血性溃疡。进一步的临床试验将为CLI患者提供新的治疗选择。

关键词: 血管再生术

图形摘要

[1]
Ali S, Kjeken R, Niederlaender C, et al. The European medicines agency review of Kymriah (Tisagenlecleucel) for the treatment of acute lymphoblastic leukemia and diffuse large B-Cell lymphoma. Oncologist 2019; 25(2): e321-7.
[http://dx.doi.org/10.1634/theoncologist.2019-0233] [PMID: 32043764]
[2]
Hoy SM. Onasemnogene Abeparvovec: First Global Approval. Drugs 2019; 79(11): 1255-62.
[http://dx.doi.org/10.1007/s40265-019-01162-5] [PMID: 31270752]
[3]
Sanada F, Taniyama Y, Muratsu J, et al. Gene-Therapeutic strategies targeting angiogenesis in peripheral artery disease. Medicines (Basel) 2018; 5(2): 31.
[http://dx.doi.org/10.3390/medicines5020031] [PMID: 29601487]
[4]
Suzuki J, Shimamura M, Suda H, et al. Current therapies and investigational drugs for peripheral arterial disease. Hypertens Res 2016; 39(4): 183-91.
[http://dx.doi.org/10.1038/hr.2015.134] [PMID: 26631852]
[5]
Morishita R, Nakamura S, Hayashi S, et al. Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy. Hypertension 1999; 33(6): 1379-84.
[http://dx.doi.org/10.1161/01.HYP.33.6.1379] [PMID: 10373220]
[6]
Hayashi S, Morishita R, Nakamura S, et al. Potential role of hepatocyte growth factor, a novel angiogenic growth factor, in peripheral arterial disease: downregulation of HGF in response to hypoxia in vascular cells. Circulation 1999; 100(19)(Suppl.): II301-8.
[http://dx.doi.org/10.1161/01.CIR.100.suppl_2.II-301] [PMID: 10567320]
[7]
Taniyama Y, Morishita R, Aoki M, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease. Gene Ther 2001; 8(3): 181-9.
[http://dx.doi.org/10.1038/sj.gt.3301379] [PMID: 11313789]
[8]
Taniyama Y, Morishita R, Hiraoka K, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model: molecular mechanisms of delayed angiogenesis in diabetes. Circulation 2001; 104(19): 2344-50.
[http://dx.doi.org/10.1161/hc4401.098470] [PMID: 11696476]
[9]
Morishita R, Sakaki M, Yamamoto K, et al. Impairment of collateral formation in lipoprotein(a) transgenic mice: therapeutic angiogenesis induced by human hepatocyte growth factor gene. Circulation 2002; 105(12): 1491-6.
[http://dx.doi.org/10.1161/01.CIR.0000012146.07240.FD] [PMID: 11914260]
[10]
Nakamura Y, Morishita R, Higaki J, et al. Hepatocyte growth factor is a novel member of the endothelium-specific growth factors: additive stimulatory effect of hepatocyte growth factor with basic fibroblast growth factor but not with vascular endothelial growth factor. J Hypertens 1996; 14(9): 1067-72.
[http://dx.doi.org/10.1097/00004872-199609000-00004] [PMID: 8986905]
[11]
Kaga T, Kawano H, Sakaguchi M, Nakazawa T, Taniyama Y, Morishita R. Hepatocyte growth factor stimulated angiogenesis without inflammation: differential actions between hepatocyte growth factor, vascular endothelial growth factor and basic fibroblast growth factor. Vascul Pharmacol 2012; 57(1): 3-9.
[http://dx.doi.org/10.1016/j.vph.2012.02.002] [PMID: 22361334]
[12]
Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998; 97: 1114-23.
[http://dx.doi.org/10.1161/01.cir.97.12.1114] [PMID: 9537336]
[13]
Gorenoi V, Brehm MU, Koch A, Hagen A. Growth factors for angiogenesis in peripheral arterial disease. Cochrane Database Syst Rev2017 2017; 6(6) CD011741
[PMID: 28594443]
[14]
MHLW Panel OKs AnGes’ gene therapy collategene for conditional approval. Available from https://pj.jiho.jp/article/239483
[15]
Shigematsu H, Yasuda K, Iwai T, et al. Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia. Gene Ther 2010; 17(9): 1152-61.
[http://dx.doi.org/10.1038/gt.2010.51] [PMID: 20393508]
[16]
Shigematsu H, Yasuda K, Sasajima T, et al. Transfection of human HGF plasmid DNA improves limb salvage in Buerger’s disease patients with critical limb ischemia. Int Angiol 2011; 30(2): 140-9.
[PMID: 21427651]
[17]
Morishita R, Aoki M, Hashiya N, et al. Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease. Hypertension 2004; 44(2): 203-9.
[http://dx.doi.org/10.1161/01.HYP.0000136394.08900.ed] [PMID: 15238569]
[18]
Morishita R, Makino H, Aoki M, et al. Phase I/IIa clinical trial of therapeutic angiogenesis using hepatocyte growth factor gene transfer to treat critical limb ischemia. Arterioscler Thromb Vasc Biol 2011; 31(3): 713-20.
[http://dx.doi.org/10.1161/ATVBAHA.110.219550] [PMID: 21183732]
[19]
Makino H, Aoki M, Hashiya N, et al. Long-term follow-up evaluation of results from clinical trial using hepatocyte growth factor gene to treat severe peripheral arterial disease. Arterioscler Thromb Vasc Biol 2012; 32(10): 2503-9.
[http://dx.doi.org/10.1161/ATVBAHA.111.244632] [PMID: 22904270]
[20]
Suda H, Murakami A, Kaga T, Tomioka H, Morishita R. Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther 2014; 12(10): 1145-56.
[http://dx.doi.org/10.1586/14779072.2014.955850] [PMID: 25190335]
[21]
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 2013; 48(3): 452-8.
[http://dx.doi.org/10.1038/bmt.2012.244] [PMID: 23208313]
[22]
Nikol S, Baumgartner I, Van Belle E, et al. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther 2008; 16: 972-8.
[http://dx.doi.org/10.1038/mt.2008.33]
[23]
Gu Y, Zhang J, Guo L, et al. A phase I clinical study of naked DNA expressing two isoforms of hepatocyte growth factor to treat patients with critical limb ischemia. J Gene Med 2011; 13(11): 602-10.
[http://dx.doi.org/10.1002/jgm.1614] [PMID: 22015632]
[24]
De Haro J, Acin F, Lopez-Quintana A, Florez A, Martinez-Aguilar E, Varela C. Meta-analysis of randomized, controlled clinical trials in angiogenesis: gene and cell therapy in peripheral arterial disease. Heart Vessels 2009; 24(5): 321-8.
[http://dx.doi.org/10.1007/s00380-008-1140-z] [PMID: 19784813]
[25]
Barć P, Antkiewicz M, Śliwa B, Baczyńska D, Witkiewicz W, Skóra JP. Treatment of critical limb ischemia by pIRES/VEGF165/HGF administration. Ann Vasc Surg 2019; 60: 346-54.
[http://dx.doi.org/10.1016/j.avsg.2019.03.013] [PMID: 31200059]
[26]
Gu Y, Cui S, Wang Q, et al. A randomized, double-blind, placebo-controlled phase II study of hepatocyte growth factor in the treatment of critical limb ischemia. Mol Ther 2019; 27: 2158-65.
[http://dx.doi.org/10.1016/j.ymthe.2019.10.017] [PMID: 31805256]
[27]
Kato N, Nemoto K, Nakanishi K, et al. Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats. Diabetes 2005; 54(3): 846-54.
[http://dx.doi.org/10.2337/diabetes.54.3.846] [PMID: 15734864]
[28]
Ajroud-Driss S, Christiansen M, Allen JA, Kessler JA. Phase 1/2 open-label dose-escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic peripheral neuropathy. Mol Ther 2013; 21(6): 1279-86.
[http://dx.doi.org/10.1038/mt.2013.69] [PMID: 23609019]
[29]
Kessler JA, Smith AG, Cha BS, et al. Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy. Ann Clin Transl Neurol 2015; 2(5): 465-78.
[http://dx.doi.org/10.1002/acn3.186] [PMID: 26000320]

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