摘要
转甲状腺素蛋白(TTR)淀粉样变是由于TTR沉积所致的系统性疾病,周围神经及心脏是主要受累脏器,严重影响患者的生活质量和生命。目前的治疗方法有限,迫切需要有新型疗法延缓或者逆转疾病进展。TTR稳定药物,如二氟尼柳和氯苯唑酸可延缓神经病变的进展,但对心肌病变是否有效仍需进一步研究。清除已形成淀粉样物质的药物(多西环素/牛磺熊去氧胆酸和抗血清淀粉样物质P抗体)目前在早期研发阶段,一旦成功,将能用于任何类型的系统性淀粉样变。基因沉默(如反义寡核苷酸和小干扰RNA)技术目前正在进行Ⅱ/Ⅲ期临床试验,初步显示能持续显著抑制突变和野生TTR合成,可能会进一步逆转淀粉样变。
Transthyretin amyloidosis （ATTR） is a muhisystemic disease resulting from deposition of insoluble TTR amyloid fi- brils in various organs and tissues. Neurological deficits or cardiac involvement are common. Therapeutic options are limited for the pa- tients. The TFR stabilizers diflunisal and tafamidis can slow disease progression in some patients with polyneuropathy ATTR, but their effects on cardiomyopathy need to be tested. The postulated synergistic effect of doxycycline and tauroursodeoxycholic acid （TUDCA） and anti-serum amyloid P （SAP） component on dissolution of amyloid is currently under investigation. Another therapeutic approach is to reduce production of the TFR by gene silencing, such as antisense oligonucleotide-based drug and small interfering RNAs. The evolv- ing treatment landscape for ATTR brings hope for further improvements in clinical outcomes for patients with this debilitating disease.
出处
《国际药学研究杂志》
CAS
CSCD
北大核心
2017年第2期140-144,共5页
Journal of International Pharmaceutical Research
基金
国家重点研发计划精准医学研究重点专项"罕见病临床队列研究"资助项目(2016YFC0901500
2016YFC0901501)
