Acivicin：治愈非洲嗜睡病的希望

对于寄生虫布氏锥虫CTP合成酶的研究使研究者离成功治愈非洲嗜睡病又近了一步。研究者使用细胞毒素acivicin使锥虫感染的小鼠免于症状的发作。

因为布氏锥虫经常改变其表面的结构，因而可避免人类对其产生免疫效应，这种寄生虫可攻击中枢神经系统，可导致精神紊乱、破坏睡眠、并且可最终导致死亡。由于寄生虫侵袭病人中枢神经系统，所以没有药物可同时治疗寄生虫感染并防止副反应。

在Umeå大学 Lars Thelander教授指导的一个项目中，科学家已在先前发现寄生虫CTP合成酶，一种产生CTP的酶类，而CTP的合成可影响寄生虫mRNA的合成，这个过程对于寄生虫的生存至关重要且是治疗疾病的靶位点。

在最新的研究中，科学家试图确定acivicin治疗时的恰当剂量，而acivicin是一种众所周知的细胞毒素，可作为肿瘤药物，抑制寄生虫CTP合成，因而最终杀灭细胞中的寄生虫。维持日常剂量的acivicin，锥虫感染的小鼠可以避免产生相应的症状，而对照组小鼠感染后几天内就会死去。

acivicin的优势是其已在临床上应用于人类。所有的临床研究对这已经确认，并且已知这种药物可以进入中枢神经系统，明显与其他的治疗药物有所区别。除外，它可以制成药片，在健康医疗受限的国家来说这种药物形式尤其重要。

Umeå大学医学化学和生物物理学教研室的研究团队希望找到acivicin合适的剂量以持续治疗寄生虫感染的小鼠。


Acivicin: Hope For a Cure For African Sleeping Sickness

Studies of the enzyme CTP synthetase in the parasite Trypanosoma brucei have brought researchers closer to a cure for African sleeping sickness. They have kept trypanosome-infected mice free of symptoms with the cell toxin acivicin.Since the parasite Trypanosoma brucei constantly changes its surface, it can avoid the immune defence of humans and invade the central nervous system, which leads to personality disturbances, sleep disruptions, and ultimately death. For patients affected by a severe Trypanosoma brucei infection in the central nervous system, there are no medicines that can treat both subspecies without incurring extremely serious side effects.
 
In a project directed by Professor Lars Thelander from Umeå University, scientists have previously discovered that the parasites’ CTP synthetase, an enzyme responsible for the production of CTP - one of the four building blocks for mRNA synthesis, a process that is critical for the survival of the parasite ¬ should be a key target for treating the disease. 

In the current publication scientists have managed to show that the proper content of acivicin, a well-known cell toxin that has previously been used as a cancer drug, can inhibit the parasite’s CTP synthetase, thereby permanently killing the trypanosomes in cell cultures. With daily doses of acivicin, trypanosome-infected mice have also been kept free of symptoms, as opposed to untreated mice that died within a few days. 

“The advantage of acivicin is that it has already been used on humans. All the clinical studies have been performed, and we know that the drug can penetrate the central nervous system, which is not the case with many other medicines for trypanosomes. What's more, it can be taken in tablet form, which is extremely important in countries with limited health-care resources,” says Artur Fijolek from Umeå University, co-author of the article. 

The research team at the Umeå University Department of Medical Chemistry and Biophysics hopes soon to be able to find the appropriate dosage of acivicin that can permanently cure the infected mice.