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A sugar-coated strategy to treat a rare neurologic disease provides a blueprint for a decoy glycan therapeutic and a potential vaccine for CoViD-19: An Editorial Highlight for "Selective inhibition of anti-MAG IgM autoantibody binding to myelin by an antigen specific glycopolymer"on page 486.
Journal of Neurochemistry ( IF 4.7 ) Pub Date : 2020-06-23 , DOI: 10.1111/jnc.15098
Lawrence Steinman 1
Affiliation  

In a rare neurologic disease known as IgM monoclonal gammopathy the immune system targets a sulfated trisaccharide known as the Human Natural Killer‐1 (HNK‐1) epitope that comprises a constituent of the myelin sheath known as MAG (myelin‐associated glycoprotein). This Editorial highlights a study by Aliu and colleagues in the current issue of the Journal of Neurochemistry, in which the investigators constructed a biodegradable poly‐l‐lysine backbone with multiple copies of this sulfated HNK‐1 trisaccharide. This decoy, poly(phenyl disodium 3‐O‐sulfo‐β‐d‐glucopyranuronate)‐(1→3)‐β‐d‐galactopyranoside, known as PPSGG, removed anti‐MAG IgM autoantibodies from the blood, while not activating the immune system. These findings provide a path for the selective removal of a pathogenic set of antibodies that target the myelin sheath resulting in neuropathy. These findings are applicable to a parallel strategy for the generation of polysaccharides similar to those present in the receptor‐binding domain of CoViD‐19, which might inhibit viral adhesion to its receptor, the angiotensin‐converting enzyme‐2 (ACE2) protein, thereby impairing cellular uptake of the virus itself. The deployment of complex polysaccharides that mimic actual COVID19 polysaccharides on the spike protein may also provide a feasible structural basis for a vaccine. Carbohydrate mimics, if conjugated to a carrier or backbone, might provoke an immune response to the spike protein. A vaccine that targets critical carbohydrates on COVID19, and then neutralizes the virus would recapitulate a successful strategy employed in other microbial vaccines, like the pneumococcal vaccines and the meningococcal vaccines. These vaccines direct an immune response to complex carbohydrates and successfully prevent life‐threatening disease. This paper provides lessons from a rare neurologic disease that may teach us strategies applicable to a global pandemic.

中文翻译:

一种治疗罕见神经系统疾病的糖衣策略为诱饵聚糖治疗剂和潜在的 CoViD-19 疫苗提供了蓝图:“通过抗原特异性糖聚合物选择性抑制抗 MAG IgM 自身抗体与髓鞘结合”的社论亮点第 486 页。

在一种称为 IgM 单克隆丙种球蛋白病的罕见神经系统疾病中,免疫系统靶向一种硫酸化三糖,称为人类自然杀伤剂-1 (HNK-1) 表位,该表位包含称为 MAG(髓磷脂相关糖蛋白)的髓鞘成分。这篇社论重点介绍了 Aliu 及其同事在本期《神经化学杂志》上的一项研究,其中研究人员构建了一个可生物降解的多聚 L-赖氨酸骨架,其中含有多份硫酸化 HNK-1 三糖。这种诱饵,聚(苯基二钠 3 - O-磺基-β- d-吡喃葡萄糖醛酸)-(1→3)-β- d- 吡喃半乳糖苷,称为 PPSGG,可从血液中去除抗 MAG IgM 自身抗体,同时不会激活免疫系统。这些发现为选择性去除一组针对导致神经病变的髓鞘的致病性抗体提供了途径。这些发现适用于生成类似于 CoViD-19 受体结合域中存在的多糖的平行策略,这可能抑制病毒与其受体血管紧张素转换酶 2 (ACE2) 蛋白的粘附,从而损害细胞对病毒本身的吸收。在刺突蛋白上部署模拟实际 COVID19 多糖的复杂多糖也可能为疫苗提供可行的结构基础。碳水化合物模拟物,如果与载体或骨架结合,可能会引发对刺突蛋白的免疫反应。针对 COVID19 上的关键碳水化合物,然后中和病毒的疫苗将概括其他微生物疫苗(如肺炎球菌疫苗和脑膜炎球菌疫苗)中采用的成功策略。这些疫苗指导对复杂碳水化合物的免疫反应,并成功预防危及生命的疾病。本文提供了一种罕见的神经系统疾病的经验教训,可以教会我们适用于全球大流行的策略。这些疫苗指导对复杂碳水化合物的免疫反应,并成功预防危及生命的疾病。本文提供了一种罕见的神经系统疾病的经验教训,可以教会我们适用于全球大流行的策略。这些疫苗指导对复杂碳水化合物的免疫反应,并成功预防危及生命的疾病。本文提供了一种罕见的神经系统疾病的经验教训,可以教会我们适用于全球大流行的策略。
更新日期:2020-08-20
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