Stamelou Maria, Boxer Adam L
Movement Disorders Clinic Second Department of Neurology Attikon Hospital Kapodistrian University of Athens Athens Greece.
Department of Movement Disorders Hygeia Hospital Athens Greece.
Mov Disord Clin Pract. 2015 Feb 2;2(1):3-5. doi: 10.1002/mdc3.12142. eCollection 2015 Mar.
In recent years, research has focused on the development of disease-modifying treatments for PSP, targeting mainly at tau dysfunction. However, the glycogen synthase kinase 3 inhibitor, tideglusib, and the microtubuli stabilizer, davunetide, both failed to show efficacy in recent double-blind, placebo-controlled studies. Despite these results, further agents targeting tau dysfunction, tau post-translational modifications, or aiming at mictorubuli stabilization are currently being investigated. Further approaches under development include agents to reduce tau levels extracellularly by active or passive immunization, antisense oligonucleotides to reduce tau concentrations, and small interfering RNAs to suppress human tau expression. However, the major limitation on the way to find disease-modifying treatments for PSP still remains the lack of biomarkers. Indeed, for all of these potential therapeutic modalities, a well-designed human trial would require validated biomarkers, without which the results of negative efficacy trials will be difficult to interpret. In this regard, PET imaging using tau-specific ligands may be proven useful in the near future. There is great hope that the next decade will bring the first effective therapy for PSP.
近年来，研究主要集中在开发针对进行性核上性麻痹（PSP）的疾病修饰疗法，主要针对tau功能障碍。然而，糖原合酶激酶3抑制剂替格列汀和微管稳定剂达武奈肽在最近的双盲、安慰剂对照研究中均未显示出疗效。尽管有这些结果，但目前仍在研究针对tau功能障碍、tau翻译后修饰或旨在稳定微管的其他药物。正在开发的进一步方法包括通过主动或被动免疫在细胞外降低tau水平的药物、降低tau浓度的反义寡核苷酸以及抑制人类tau表达的小干扰RNA。然而，寻找PSP疾病修饰疗法的主要限制仍然是缺乏生物标志物。事实上，对于所有这些潜在的治疗方式，精心设计的人体试验都需要经过验证的生物标志物，没有这些标志物，阴性疗效试验的结果将难以解释。在这方面，使用tau特异性配体的正电子发射断层扫描（PET）成像在不久的将来可能会被证明是有用的。人们非常希望未来十年能带来第一种有效的PSP治疗方法。
