Department of Neurology, Institute for Neurological Research Dr. Raúl Carrea, FLENI, Montañeses 2325, 1428, Buenos Aires, Argentina,
Curr Treat Options Neurol. 2014 Jun;16(6):296. doi: 10.1007/s11940-014-0296-3.
Epidemiological studies suggest that autoimmune diseases, such as multiple sclerosis (MS), are less frequent in individuals who are helminth carriers. This observation has been tested in murine models of colitis, MS, type 1 diabetes and asthma. In each case, mice colonized with helminths show protection from disease. This apparent down-modulation of inflammatory response resulting from helminth infection has triggered interest in exploring the potential clinical efficacy of controlled helminth infection in patients suffering from autoimmune diseases. To date, clinical trials using helminth therapy (Trichura suis ova [TSO] or Necator americanus larvae) in MS have been small, safety-oriented trials of short duration, attempting to reproduce and confirm epidemiological and experimental data. Thus far, no adverse events related to therapeutic helminth infection have been observed. Nonetheless, there is a clear need for caution when considering such approaches. Some preliminary clinical, magnetic resonance imaging and immunological outcomes using TSO have been encouraging. Nevertheless, results should be interpreted with caution as the number of individuals studied was small and duration of follow up limited. Longer studies, monitoring safety and objective outcome measures are necessary to assess this novel therapeutic strategy in a more definitive fashion. An alternative approach to use of live helminth infections might arise from identification of helminth-derived immunomodulatory molecules mimicking the protective effects of parasite infection, i.e. capable of altering immune responses and, therefore, the course of autoimmune diseases. Although positive results from administering parasite products in mouse models of autoimmunity have been reported, much remains to be explored before the field can move from experimental animal models to application in clinical practice. To the best of my knowledge, parasite-derived molecules have not yet been administered as treatment for any autoimmune disease in humans. At this time, it is strongly recommended that live helminth or ova parasites be administered only to individuals participating in strictly monitored, controlled clinical trials.
流行病学研究表明,患有多发性硬化症(MS)等自身免疫性疾病的个体中,寄生虫携带者的发病率较低。这一观察结果在结肠炎、MS、1 型糖尿病和哮喘的鼠模型中得到了验证。在每种情况下,感染寄生虫的小鼠均表现出对疾病的保护作用。寄生虫感染导致的炎症反应明显下调,这引发了人们对探索在自身免疫性疾病患者中进行受控寄生虫感染的潜在临床疗效的兴趣。迄今为止,使用寄生虫疗法(猪鞭虫卵[TSO]或美洲钩虫幼虫)治疗 MS 的临床试验规模较小,都是短期、以安全性为导向的试验,旨在复制和确认流行病学和实验数据。到目前为止,尚未观察到与治疗性寄生虫感染相关的不良事件。尽管如此,在考虑这些方法时仍需谨慎。一些使用 TSO 的初步临床、磁共振成像和免疫学结果令人鼓舞。然而,由于研究人数较少且随访时间有限,结果应谨慎解释。需要进行更长时间的研究,监测安全性和客观的结局指标,以更明确地评估这种新的治疗策略。另一种替代方法可能是使用寄生虫来源的免疫调节分子,这些分子模拟寄生虫感染的保护作用,即能够改变免疫反应,从而改变自身免疫性疾病的进程。尽管已经报道了在自身免疫性疾病的小鼠模型中给予寄生虫产物的阳性结果,但在该领域能够从实验动物模型转移到临床实践之前,仍有许多工作需要探索。据我所知,寄生虫衍生的分子尚未被用于治疗任何人类自身免疫性疾病。此时,强烈建议仅将活寄生虫或卵寄生虫给予参与严格监测、对照临床试验的个体。