NEXGEN-PD

帕金森病（Parkinson's Disease，PD）是一种主要的神经退行性疾病，目前尚无能够改变疾病病理的既定治疗方法，也没有早期诊断的手段。靶向aSyn聚集体的疫苗是PD疾病修饰治疗的一种有前途的途径，但目前这一代PD疫苗使用的是常规制剂，其免疫原性有限，需要大量佐剂才能达到疗效。NEXGEN专有的WISIT疫苗平台是第一种新型的免疫缀合物疫苗（GNCV），其通过皮内注射和专门配制，以利用皮肤树突细胞（DC）产生比传统疫苗更强和更特异的免疫反应。这些更强的免疫应答允许大量减少佐剂，同时增加治疗效果。NEXGEN将鉴定和筛选靶向aSyn的候选WISIT构建体（PD-WISIT），并开发一种新型的基于细胞外囊泡（EV）的生物标志物测定法，该测定法能够使用液体活检进行PD的早期诊断，适用于现场护理。PD-WISIT的安全性和有效性将在临床前得到证实，然后与新型EV生物标志物检测一起沿着进行首次人体I/Ib期临床试验。NEXGEN的结果将是早期PD的廉价有效的疾病修饰治疗和诊断和指导前驱/早期PD治疗的新型生物标志物测定的非凡成就。此外，GNCV技术将在临床上得到证明，该技术有可能对治疗各种其他疾病产生变革性影响，从而对数百万人的健康产生深远影响。

Parkinson’s Disease (PD) is a major neurodegenerative disorder with no established treatment modalities capable of modifying diseasepathology, and no means of early diagnosis. Vaccines targeting aSyn aggregates are a promising route to disease-modifying therapyfor PD, but the current generation of PD vaccines utilise conventional formulations, which are limited in their immunogenicity andrequire substantial quantities of adjuvant to achieve efficacy. NEXGEN’s proprietary WISIT vaccine platform is the first of the novelclass of gluconeoconjugate vaccines (GNCVs), which are administered intradermally and specifically formulated to leverage skindendritic cells (DCs) to generate substantially stronger and more specific immune responses than conventional vaccines. These strongerimmune responses allow substantial reduction in adjuvants, while simultaneously increasing therapy efficacy. NEXGEN will identify andcharacterise candidate WISIT constructs targeting aSyn (PD-WISITs) and develop a novel extracellular vesicle (EV)-based biomarkerassay that enables early diagnosis of PD using liquid biopsies, suitable for point of care use. Safety and efficacy of PD-WISITs will bedemonstrated preclinically, before being translated to first-in-human Phase I/Ib clinical trials, along with the novel EV-based biomarkerassay. The results of NEXGEN will be the extraordinary accomplishments of cheap and effective disease-modifying treatment of earlyPD and a novel biomarker assay to diagnose and guide prodromal/early PD treatment. Further still, GNCV technology will be clinicallydemonstrated, which hasthe potential to be transformative to the treatment of a wide range of additional diseases, resulting in far-reachingimpacts to the health of millions.