体外扩增自体调节性T细胞治疗肌萎缩侧索硬化症的安全性和疗效研究

Preliminary Study on the Treatment of Amyotrophic Lateral Sclerosis with Expanded Autoregulatory T Cells in Vitro

目的 探索体外扩增的自体调节性T细胞(Treg)治疗肌萎缩侧索硬化症(ALS)的临床安全性和疗效。方法 收集2018年9月至2020年12月就诊符合入组标准的65例ALS患者,随机分为Treg组(33例)和安慰剂组(32例)。主要观察目标为两组患者的治疗安全性,观察治疗前(治疗前3个月-基线)、治疗结束后(9个月治疗结束-基线)修订版ALS功能评定量表(ALSFRS-R)均数变化;次要观察目标为Appel ALS评定量表(AALS)、Rasch构建的ALS整体残疾量表(ROADS)、用力肺活量(FVC)均数变化、死亡和气管切开病例数。结果 (1)本研究达到了主要安全终点,治疗安全。(2)从治疗前3个月至基线,Treg组(-3.77分/3个月)和安慰剂组(-3.22分/3个月)的ALSFRS-R均数下降相似(P>0.05);从基线至6个治疗周期结束时,安慰剂组ALSFRS-R均数(-4.81分/9个月)较Treg组(-0.39分/9个月)显著下降(P<0.01)。(3)Treg组AALS、ROADS、FVC均数治疗后变化均优于安慰剂组。结论 ALS患者接受自体Treg细胞治疗安全性较好,且短期内临床症状明显改善。

Aim To explore the clinical safety and efficacy of autologous regulatory T cells(Treg)expanded in vitro in the treatment of amyotrophic lateral sclerosis(ALS).Methods Sixty-five patients with ALS who met the inclusion criteria from September 2018 to December 2020 were collected and randomly divided into a Treg group(33 cases)and a placebo group(32 cases).The safety of treatment was mainly observed.The mean changes of the revised ALS Functional Rating Scale(ALSFRS-R)were observed before the treatment(baseline-3 months before the treatment)and after the treatment(9 months after the treatment-baseline).Appel ALS Rating Scale(AALS),Rasch's ALS Overall Disability Scale(ROADS),mean change of forced vital capacity(FVC),death and tracheotomy were the secondary observation objectives.Results(1)This study reached the main safe end point and the treatment was safe.(2)From the 3 months before the treatment to the baseline,the mean decrease of ALSFRS-R in Treg group(-3.77 points/3 months)and placebo group(-3.22 points/3 months)was similar(P>0.05);From baseline to the end of the six treatment cycles,the mean number of ALSFRS-R in the placebo group(-4.81 points/9 months)was significantly lower than that in the Treg group(-0.39 points/9 months)(P<0.01).(3)The changes of AALS,ROADS and FVC in Treg group after the treatment were better than those in placebo group.Conclusion It is safe for ALS patients to receive autologous Treg cells treatment,and the clinical symptoms are significantly improved in a short time.