观察一种促进神经损伤修复的药物组合物治疗运动神经元病(MND)患者的疗效。

选取2016年9月至2018年4月江苏大学附属武进医院、苏州高新区人民医院及常州华森康复医院收治的60例MND患者为研究对象进行前瞻性自身对照研究，其中男性39例，女性21例；年龄26～73岁，平均年龄(52.87 ± 9.78)岁。在常规综合治疗基础上，将一种促进神经损伤修复的药物组合物[精氨酸1.5～5 g，异亮氨酸1.5～5 g，亮氨酸2.5～7.5 g，赖氨酸1.5～5 g，蛋氨酸0.25～1.5 g，苯丙氨酸0.25～1.5 g，苏氨酸1.5～5 g，色氨酸0.25～1.5 g，缬氨酸2.5～7.5 g，组氨酸1.5～4 g，甘氨酸1.5～4 g，丙氨酸1.5～5 g，脯氨酸1.5～4 g，天冬酰胺0.05～1.5 g，半胱氨酸0.05～1.5 g，谷氨酸1.5～5 g，丝氨酸0.25～2.5 g，酪氨酸0.05～1.5 g，L～鸟氨酸0.25～4 g，天冬氨酸0.5～2.5 g；维生素(维生素B₁ 1～2 mg，维生素B₂ 1～2 mg，维生素B₆ 3～10 g，维生素C 1～3 g)]配制在1个三升输液袋内进行静脉输注，1次/d，28 d为1个疗程，休息2周后行第2个疗程，持续治疗时间≥4个疗程(或6个月)。观察患者治疗前后及随访的肌萎缩侧索硬化症改良功能评分量表(ALSFRS-R)评分、疾病进展率及临床表现等变化情况以评估治疗效果。同时记录治疗过程中患者出现的不良反应，以评价新疗法的安全性。

本组60例MND患者中死亡3例(5.00%)，均为疾病晚期呼吸衰竭。肌肉萎缩好转、肌力增加6例(10.00%)，舌肌萎缩、构音障碍好转1例(1.67%)，流涎好转2例(3.33%)，吞咽功能改善1例(1.67%)，四肢活动度增加4例(6.67%)，1例(1.67%)不能独立行走的患者可辅助蹲起和独自缓慢行走。各阶段ALSFRS-R评分：首次门诊(n＝60)的ALSFRS-R评分为15.0～48.0分，平均(32.21±8.70)分；治疗4个疗程(或6个月)时(n＝60)的评分为3.0～45.0分，平均(28.32±9.56)分；末次治疗时(n＝59)评分为3.0～48.0分，平均(28.36±9.50)分。治疗4个疗程(或6个月)时(n＝60，t＝－3.950，P<0.05)和末次治疗时(n＝59，t＝3.845，P<0.05)的ALSFRS-R评分均低于治疗前，差异均有统计学意义。但完成6个月治疗时有19例患者(31.67%)的ALSFRS-R评分上升，2例(3.33%)评分不变，且有61.67%(37/60)的患者疾病进展率较前下降；延长治疗时间后，评分下降患者的占比降低至57.63%(34/59)。对28例停药患者进行2～12月的随访发现：在完成一定疗程的规范化治疗后，即使患者停止用药，仍然可见到较为长时间的持续疗效：25.93%(7/28)停药患者的ALSFRS-R评分较治疗前有所上升；末次随访疾病进展率仍然低于治疗前[0.50(0.42)分/月比0.56(0.60)分/月，Z＝-2.691，P<0.05)]，且74.07%(20/27)停药患者的疾病进展率较治疗前减缓。但因为停止治疗后，疗效难以在长时间内持续维持在较好水平[74.07%(20/27)患者的末次随访ALSFRS-R低于末次治疗]，因此持续的巩固治疗是有必要的。

该促进神经损伤修复的药物组合物能在整体上为MND患者提供机体新陈代谢的底物、辅酶与强劲的动能，从而延缓疾病发展，改善病情与临床症状。新疗法的确无毒无害无副作用，重复性好。

To observe the efficacy of a pharmaceutical composition for promoting nerve repair in patients with motor neuron disease (MND).

A prospective, self-controlled study of 60 patients with MND admitted to Wujin Hospital affiliated to Jiangsu University, the People’s Hospital of SND and Changzhou Huasen Rehabilitation Hospital from September 2016 to April 2018 was conducted, including 39 males and 21 females, aged from 26 to 73 years, with the average age(52.87 ± 9.78)years. On the basis of conventional comprehensive treatment, the above pharmaceutical composition [main components: arginine 1.5-5 g, isoleucine 1.5-5 g, lysine 2.5-7.5 g, methionine 0.5-1.5 g, phenylalanine 0.5-5 g, tryptophan 0.5-1.5 g, valine 2.5-7.5 g, histidine 1.5-4 g, glycine 1.5-4 g, alanine 1.5-5 g, proline 1.5-4 g, asparagine 0.05-1.5 g, cysteine 0.05-1.5 g, cysteine 1.5-5 g, serine 0.25-2.5 g, tyrosine 0.05-1.5 g, L-ornithine 0.25-4 g, aspartic acid 0.5-2.5 g and vitamins (vitamin B₁ 1-2 mg, vitamin B₂ 1-2 mg, vitamin B₆ 3-10 g, vitamin C 1-3 g)] was prepared in a three-liter infusion bag for intravenous infusion, once a day, 28 days for 1 course of treatment. After a 2-week interval, the next course of treatment was repeated. And the continuous treatment lasted at least for 4 courses (or 6 months). The changes of amyotrophic lateral sclerosis modified functional rating scale-revised (ALSFRS-R), disease progression rate and clinical manifestation were observed in all patients pre- and post-treatment to evaluate the therapeutic effect. The adverse reactions during the treatment were also recorded to evaluate the safety of the new therapy.

Three patients (5.00%) died of the advanced respiratory failure. Symptoms of muscle atrophy and muscle strength were improved in 6 cases (10.00%), tongue muscle atrophy and dysarthria were improved in 1 case (1.67%), salivation were improved in 2 cases (3.33%), the swallowing function was improved in 1 case (1.67%), and limb activity were improved 4 cases (6.67%). 1 patient (1.67%) who could not walk independently could squat and stand up with other’s assistance and walked slowly and independently. For the outpatients (n=60), ALSFRS-R scores ranged from 15.0 to 48.0, with an average of (32.21 ± 8.70) points. After 4 courses (or 6 months) (n=60), the score was 3.0~45.0 points, with an average of (28.32 ± 9.56) points. The score after final treatment (n = 59) was 3.0~48.0 points, with an average of (28.36 ± 9.50) points. Compared with the result before treatment, the ALSFRS-R scores were both decreased after the 4 courses (or 6 months) (n=60, t=-3.950, P<0.05) and the last treatment (n=59, t=3.845, P<0.05). However, after the 6-month treatment, 19 patients (31.67%) had an increase in ALSFRS-R score, 2 patients (3.33%) had the same score, and 61.67% (37/60) had a lower disease progression rate. After a prolonged treatment, the proportion of patients with decreased scores went down to 57.63% (34/59). A follow-up of 2 to 12 months in 28 patients showed that after a certain course of treatment was completed, a long-term sustained effect was observed even if the patient stopped taking the drug; the ALSFRS-R score increased in 25.93% (7/28) compared with that before treatment. And the disease progression rate at the last follow-up was still lower than that before treatment [0.50 (0.42) points/month to 0.56 (0.60) points/month, Z=-2.691, P<0.05). ], and the disease progression rate of 74.07% (20/27) discontinued patients was slower than that before treatment. However, because the effect was difficult to maintain a good level for a long time after stopping treatment [74.07% (20/27) patients with the last follow-up ALSFRS-R was lower than that of the last treatment], a continuous consolidation treatment was necessary.

Clinically, the pharmaceutical composition for promoting nerve damage repair can provide the substrate, coenzyme and strong kinetic energy for MND patients, thus delaying the development of the disease and improving the condition and clinical symptoms. The new treatment is indeed non-toxic, harmless, less side effects and reproducible.