Schipper Hyman M, Arnold Douglas, GrandʼMaison Francois, Melmed Calvin, Moore Fraser, Levental Mark, Su Haixiang, Constantin Michel, Stril Jean-Louis, Godin Jean
Departments of *Neurology and Neurosurgery, and †Medicine (Geriatrics), McGill University; ‡Lady Davis Institute for Medical Research, Jewish GeneralHospital; §NeuroRx Research; ∥Hôpital Charles Lemoyne; ¶Department of Radiology, Jewish General Hospital; and #Teva Neuroscience Canada, Montreal,Quebec, Canada.
Clin Neuropharmacol. 2015 Jul-Aug;38(4):127-31. doi: 10.1097/WNF.0000000000000090.
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system where inflammation and neurodegeneration play key roles. Mounting evidence implicates oxidative stress in the development of irreversible neuronal and glial injury in this condition. N-acetylcysteine (NAC) is a sulfhydryl amino acid derivative with antioxidant and antiapoptotic properties. Administration of NAC to mice attenuated the induction of or improved experimental autoimmune encephalomyelitis (an MS model).
We performed an open-label study to explore the tolerability and safety of the combination of glatiramer acetate (GA) and NAC in patients with relapsing-remitting multiple sclerosis at the outpatient MS clinics of the Jewish General Hospital and Hôpital Charles Lemoyne, Montreal, Canada. Seven patients with relapsing-remitting multiple sclerosis with at least one T1 gadolinium-enhancing lesion on screening magnetic resonance imaging were recruited. Treatment consisted of a 10-week run-in period followed by 36-week treatment with a combination of GA 20 mg subcutaneously once daily plus NAC 2.5 g orally twice daily. Outcome measures included safety and tolerability, redox biochemistry, and magnetic resonance imaging effect.
Treatment with the combination of GA and NAC was safe and well tolerated.
In light of the favorable safety profile, an efficacy-demonstrating study may be considered.
多发性硬化症（MS）是一种中枢神经系统的自身免疫性疾病，炎症和神经退行性变在其中起关键作用。越来越多的证据表明氧化应激在这种情况下不可逆的神经元和神经胶质损伤的发展中起作用。N-乙酰半胱氨酸（NAC）是一种具有抗氧化和抗凋亡特性的巯基氨基酸衍生物。给小鼠施用NAC可减轻实验性自身免疫性脑脊髓炎（一种MS模型）的诱导或改善其病情。
我们在加拿大蒙特利尔犹太总医院和查尔斯·勒莫因医院的门诊MS诊所进行了一项开放标签研究，以探索醋酸格拉替雷（GA）和NAC联合使用在复发缓解型多发性硬化症患者中的耐受性和安全性。招募了7例复发缓解型多发性硬化症患者，其在筛查磁共振成像上至少有一个T1钆增强病灶。治疗包括为期10周的导入期，随后是36周的治疗，联合使用GA 20 mg皮下注射每日一次加NAC 2.5 g口服每日两次。结果指标包括安全性和耐受性、氧化还原生物化学以及磁共振成像效果。
GA和NAC联合治疗安全且耐受性良好。
鉴于良好的安全性，可考虑进行一项疗效验证研究。
