光遗传学治疗对多发性硬化症患者的治疗潜力

Mohamed M. El Koussy, N. Jadavji
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引用次数: 1

摘要

已发现(Harbo,Gold,&Tintoré,2013)。从遗传学上讲,多发性硬化症的最佳特征是人类白细胞抗原(HLA)基因座的突变,这会导致T细胞的异常抗原识别,从而攻击髓鞘蛋白(Raffel等人,2016)。这些发现并不是决定性的,因为许多其他参与免疫作用的基因也被发现在导致MS中发挥作用。环境风险因素包括吸烟、阳光照射和维生素D缺乏(Raffel等人,2016)。目前,还没有治愈多发性硬化症的治疗方法(Ziemssen等人,2016)。相反,治疗的目标是症状管理,以提高患者的生活质量。其中包括高剂量皮质类固醇,如甲基强的松龙(Jongen等人,2016),疾病改良治疗(DMTs),如干扰素β-1a、干扰素β-1b、阿仑单抗、芬戈利莫和那他珠单抗(Carrithers等人,2014;Gajofatto和Benedetti,2015),以及神经康复(Dasari、Wootla、Warrington和Rodriguez,2016)。所有这些治疗方案都有不良影响,或者从长远来看不是特别有效(Jongen等人,2016;Ontaneda、Fox和Chataway,2015;Schäcke、Döcke和Asadullah,2002年;Ziemssen等人,2016)。人们非常需要更有效的新治疗方案,同时减少不良副作用。对多发性硬化症患者的潜在治疗方法可能是光遗传学的治疗应用。光遗传学是一种利用光感受器选择性激活神经元的新方法(Hegeman&Nagel,2013)。这些受体的遗传密码以病毒或非病毒的方式传递到感兴趣的细胞上表达。一旦表达,引言多发性硬化症(MS)是一种慢性自身免疫性疾病,会导致整个神经系统的局灶性和弥漫性神经变性和髓鞘形成(Kolasinski等人,2012;Siffrin、Vogt、Radbruch、Nitsch和Zipp,2010)。在其最常见的形式,复发-缓解型多发性硬化症中,其特征是高炎症水平,导致复发和缓解的持续循环(Raffel,Wakerley,&Nicholas,2016)。这些复发被称为恶化,可能以新症状或旧症状恶化的形式出现,这些症状主要是神经系统症状,如视觉障碍和失衡,在几天或几周内恶化,然后自发恢复(Wingerchuk等人,2014)。其他常见症状包括认知障碍、膀胱控制丧失、腿部无力和感觉症状(Raffel等人,2016)。遗传和环境因素都在MS的发展中发挥作用;然而,与该疾病的特定联系并没有对多发性硬化症患者进行光遗传学治疗的潜力
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Therapeutic potential of optogenetic treatment for individuals with multiple sclerosis
been found (Harbo, Gold, & Tintoré, 2013). Genetically, MS is best characterized by a mutation on the human leukocyte antigen (HLA) gene locus, which causes abnormal antigen recognition of T cells leading to attacks on myelin proteins (Raffel et al., 2016). These findings have not been conclusive, as many other genes involved in immunological roles have also been found to play a role in contributing to MS. Environmental risk factors include smoking ,sunlight exposure, and vitamin D deficiency (Raffel et al., 2016). Currently, there are no treatments that cure MS (Ziemssen et al., 2016). Instead, treatments target symptom management to increase patients’ quality of life. These include high doses of corticosteroids such as methylprednisolone (Jongen et al., 2016), Disease modifying Treatments (DMTs) such as interferon β-1a, interferon β-1b, alemtuzumab, fingolimod and natalizumab (Carrithers et al., 2014; Gajofatto & Benedetti, 2015), and neuro-rehabilitation (Dasari, Wootla, Warrington, & Rodriguez, 2016). All of these treatment options have adverse effects or are not particularly effective in the long term (Jongen et al., 2016; Ontaneda, Fox, & Chataway, 2015; Schäcke, Döcke, & Asadullah, 2002; Ziemssen et al., 2016). There is a considerable need for new treatment options that are more effective, while reducing the adverse side-effects. A potential therapy for MS-affected individuals may be the therapeutic application of optogenetics. Optogenetics is a novel method that utilizes photoreceptors to selectively activate neurons (Hegemann & Nagel, 2013). The genetic code of these receptors is delivered either virally or nonvirally to be expressed on the cells of interest. Once expressed, Introduction Multiple Sclerosis (MS) is a chronic autoimmune disease that leads to focal and diffuse neurodegenration and myelination throughout the nervous system (Kolasinski et al., 2012; Siffrin, Vogt, Radbruch, Nitsch, & Zipp, 2010). In its most common form, relapseremitting MS, it is characterized by high inflammation levels that lead to a continuous cycle of relapse and remission (Raffel, Wakerley, & Nicholas, 2016). These relapses, called exacerbations, may come in the form of new or worsening of old symptoms that are largely neurological such as visual impairment and imbalance that worsen over days or weeks, then recover spontaneously (Wingerchuk et al., 2014). Other common symptoms are cognitive impairment, loss of bladder control, leg weakness and sensory symptoms (Raffel et al., 2016). Genetic and environmental factors both have a role in MS development; however, a specific link to the disease has not Therapeutic Potential of Optogenetic Treatment for Individuals with Multiple Sclerosis
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