Ozanimod
这是一种正在研发中的新型口服的选择性鞘氨醇 1 磷酸 1 (S1PR1) 和 5 (S1PR5) 受体调节剂,适用于免疫炎症性疾病,包括复发性 MS。III 期临床试验正在进行中。[104]ClinicalTrials.gov. A multi-site, open-label extension trial of oral RPC1063 in relapsing multiple sclerosis. June 2017. https://clinicaltrials.gov (last accessed 12 July 2017).https://clinicaltrials.gov/ct2/show/NCT02576717
干细胞治疗
造血干细胞移植 (HSCT) 的前提是可以清除 MS 患者失调、自身反应性的免疫系统,而换成新的、耐受的免疫系统。[105]Gosselin D, Rivest S. Immune mechanisms underlying the beneficial effects of autologous hematopoietic stem cell transplantation in multiple sclerosis. Neurotherapeutics. 2011;8:643-649.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250285/http://www.ncbi.nlm.nih.gov/pubmed/21904792?tool=bestpractice.com对 RRMS 患者临床试验的初步报告已发布。在小部分患有非常活跃的 RRMS 的患者中,免疫抑制后进行 HSCT 可改善神经系统功能。[106]Nash RA, Hutton GJ, Racke MK, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report. JAMA Neurol. 2015;72:159-169.http://archneur.jamanetwork.com/article.aspx?articleid=2084840http://www.ncbi.nlm.nih.gov/pubmed/25546364?tool=bestpractice.com[107]Burt RK, Balabanov R, Han X, et al. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2015;313:275-284.http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17986http://www.ncbi.nlm.nih.gov/pubmed/25602998?tool=bestpractice.com一项多中心观察性研究纳入了主要包含进行性 MS 的患者队列,研究报告在接受自体干细胞移植的患者中有近一半患者的无进展生存期为 5 年。[108]Muraro PA, Pasquini M, Atkins HL, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74:459-469.http://www.ncbi.nlm.nih.gov/pubmed/28241268?tool=bestpractice.com目前正处于研究中的其他干细胞使用方案包括使用间充质干细胞、[109]Cohen JA. Mesenchymal stem cell transplantation in multiple sclerosis. J Neurol Sci. 2013;333:43-49.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624046/http://www.ncbi.nlm.nih.gov/pubmed/23294498?tool=bestpractice.com胎盘干细胞[110]Lublin FD, Bowen JD, Huddlestone J, et al. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study. Mult Scler Relat Disord. 2014;3:696-704.http://www.msard-journal.com/article/S2211-0348(14)00101-1/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/25891548?tool=bestpractice.com以及鞘内给药。[111]ClinicalTrials.gov. Intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NP) in patients with multiple sclerosis. October 2016. http://clinicaltrials.gov (last accessed 12 July 2017).https://clinicaltrials.gov/ct2/show/NCT01933802
利妥昔单抗
利妥昔单抗获批用于其他疾病,关于用于治疗 MS 的临床试验正在进行中。目前关于此药物,已有一些积极的临床试验数据。[112]He D, Guo R, Zhang F, et al. Rituximab for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev. 2013;(12):CD009130.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009130.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24310855?tool=bestpractice.com
疫苗试验
多项针对 MS 治疗(而非预防)的疫苗试验正在展开。
深部脑刺激
已在小范围的研究群体中对存在震颤的 MS 患者进行了行深部脑刺激的评估。其结果是多变的,患者应当慎重选择行 DBS 治疗。结果是可变的,应当慎重选择进行 DBS 的患者。[113]Timmermann L, Deuschl G, Fogel W, et al; Deep Brain Stimulation Association. Deep brain stimulation for tremor in multiple sclerosis: consensus recommendations of the German Deep Brain Stimulation Association [in German]. Nervenarzt. 2009;80:673-677.http://www.ncbi.nlm.nih.gov/pubmed/19471902?tool=bestpractice.com[114]Torres CV, Moro E, Lopez-Rios AL, et al. Deep brain stimulation of the ventral intermediate nucleus of the thalamus for tremor in patients with multiple sclerosis. Neurosurgery. 2010;67:646-651.http://www.ncbi.nlm.nih.gov/pubmed/20647964?tool=bestpractice.com
口服大麻属提取物
一项随机、双盲、安慰剂对照、III 期试验已经证明,口服大麻属提取物在治疗稳定期 MS 患者中的肌肉僵硬方面优于安慰剂。[115]Zajicek JP, Hobart JC, Slade A, et al. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012;83:1125-1132.http://jnnp.bmj.com/content/83/11/1125.longhttp://www.ncbi.nlm.nih.gov/pubmed/22791906?tool=bestpractice.com使用大麻属提取物的不良反应与大麻素的已知副作用一致。关于在神经系统疾病中使用医用大麻的系统性综述表明,口服大麻属提取物在减少痉挛、中枢性疼痛和痛性痉挛方面有疗效。严重不良精神症状的风险为 1%,应当仔细考虑使用的风险和获益。[116]Koppel BS, Brust JC, Fife T, et al; Guideline Development Subcommittee, American Academy of Neurology. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders. Neurology. 2014;82:1556-1563.http://www.neurology.org/content/82/17/1556.longhttp://www.ncbi.nlm.nih.gov/pubmed/24778283?tool=bestpractice.com