Doh-ura Katsumi
Division of Prion Biology, Tohoku University Graduate School of Medicine.
Rinsho Shinkeigaku. 2009 Nov;49(11):946-8. doi: 10.5692/clinicalneurol.49.946.
There is no established treatment for prion diseases; however, recently several drug candidates, including pentosan polysulfate and doxycycline, have been clinically used on a trial basis to prevent accumulation of abnormal prion protein in the brain. So far the outcome of the trials is still very far from the goal where a complete cure of the diseases is expected. In order to bridge the gap between the reality and the ideal, the followings are suggested. First, combination therapy needs to be developed against multi-targets: inhibition of prion replication; degradation and scavengery of prion; inhibition of prion-related neurodegeneration. Secondly, preclinical diagnostic means, by which healthy prion-carriers can be revealed before the onset of the diseases, should be explored for earlier therapeutic interventions. The last is to disclose intrinsic disease susceptibility factors and environmental factors, both of which could solely or jointly facilitate in suppressing prion replication and disease progress. Exploitation of these items should be tough but will be deserved for overcoming the fatal diseases.
目前尚无针对朊病毒疾病的确立疗法;然而,最近包括戊聚糖多硫酸盐和强力霉素在内的几种候选药物已在临床上进行试验性使用,以防止异常朊病毒蛋白在大脑中积累。到目前为止,试验结果距离预期的完全治愈该疾病的目标仍相差甚远。为了弥合现实与理想之间的差距,建议如下。首先,需要开发针对多靶点的联合疗法:抑制朊病毒复制;降解和清除朊病毒;抑制与朊病毒相关的神经退行性变。其次,应探索临床前诊断方法,以便在疾病发作前发现健康的朊病毒携带者,从而进行更早的治疗干预。最后是揭示内在的疾病易感性因素和环境因素,这两者单独或共同都可能有助于抑制朊病毒复制和疾病进展。开发这些项目虽然艰巨,但对于攻克这些致命疾病来说是值得的。