Sienkiewicz Dorota, Kułak Wojciech, Okurowska-Zawada Bożena, Paszko-Patej Grażyna, Wojtkowski Janusz, Sochoń Karolina, Kalinowska Anna, Okulczyk Kamila, Sienkiewicz Jerzy, McEachern Edward
Department of Pediatric Rehabilitation, Medical University of Bialystok, Białystok, Poland.
Białystok Technical University, Białystok, Poland.
Front Neurol. 2017 Oct 26;8:566. doi: 10.3389/fneur.2017.00566. eCollection 2017.
The current standard treatment for patients with Duchenne muscular dystrophy (DMD) involves corticosteroids. Granulocyte colony-stimulating factor (G-CSF) induces the proliferation of satellite cells and myoblasts and, in turn, muscle regeneration. Beneficial effects of G-CSF were also described for skeletal muscle disorders.
We assessed the safety and effects of using G-CSF to promote muscle strength in patients with DMD.
Inclusion criteria were as follows: patients aged 5-15 years with diagnosed with DMD confirmed by genetic test or biopsy. Fourteen patients were treated with steroids, and their use was not changed in this study. Diagnoses were confirmed by genetic tests: deletions were detected in 11 patients and duplications in 5 patients. Nineteen 5- to 15-year-old patients diagnosed with DMD-9 were in wheelchairs, whereas 10 were mobile and independent-completed an open study. Participants received a clinical examination and performed physiotherapeutic and laboratory tests to gage their manual muscle strength, their isometric force using a hand dynamometer, and aerobic capacity [i.e., 6-min walk test (6MWT)] before and after therapy. Each participant received G-CSF (5 µg/kg/body/day) subcutaneously for five consecutive days during the 1st, 2nd, 3rd, 6th, and 12th month. Laboratory investigations that included full blood count and biochemistry were performed. Side effects of G-CSF treatment were assessed during each visit. During each cycle of G-CSF administration in the hospital, rehabilitation was also applied. All patients received regular ambulatory rehabilitation.
The subcutaneous administration of G-CSF improved muscle strength in participants. We recorded a significant increase in the distance covered in the 6MWT, either on foot or in a wheelchair, increased muscle force in isometric force, and a statistically significant decrease in the activity of the muscle enzyme creatine kinase after nearly every cycle of treatment. We observed no side effects of treatment with G-CSF.
Our findings suggest that G-CSF increases muscle strength in patients with DMD, who demonstrated that G-CSF therapy is safe and easily tolerable.
目前杜氏肌营养不良症（DMD）患者的标准治疗方法包括使用皮质类固醇。粒细胞集落刺激因子（G-CSF）可诱导卫星细胞和成肌细胞增殖，进而促进肌肉再生。G-CSF对骨骼肌疾病也有有益作用。
我们评估了使用G-CSF提高DMD患者肌肉力量的安全性和效果。
纳入标准如下：年龄在5至15岁、经基因检测或活检确诊为DMD的患者。14例患者接受类固醇治疗，本研究中其用药情况未改变。通过基因检测确诊：11例患者检测到基因缺失，5例患者检测到基因重复。19例年龄在5至15岁、诊断为DMD-9的患者需要借助轮椅行动，而10例能够自主行动的患者完成了一项开放性研究。参与者在治疗前后接受临床检查，并进行物理治疗和实验室检测，以评估其徒手肌力、使用握力计测量的等长肌力和有氧运动能力[即6分钟步行试验（6MWT）]。每位参与者在第1、2、3、6和12个月连续5天皮下注射G-CSF（5μg/kg/天）。进行包括全血细胞计数和生化检查在内的实验室检查。每次就诊时评估G-CSF治疗的副作用。在医院进行G-CSF给药的每个周期中，还会进行康复治疗。所有患者均接受定期门诊康复治疗。
皮下注射G-CSF可提高参与者的肌肉力量。我们记录到，几乎在每个治疗周期后，无论是步行还是借助轮椅进行6MWT所覆盖的距离均显著增加，等长肌力增强，肌肉酶肌酸激酶的活性在统计学上显著降低。我们未观察到G-CSF治疗的副作用。
我们的研究结果表明，G-CSF可增强DMD患者的肌肉力量，证明G-CSF治疗安全且易于耐受。
