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

AND-PD investigates causative mechanisms of anxiety (with or without depression) as a non-motor co-morbidity of Parkinson’s Disease (PD) and aims to understand the functional and pathological changes in the brainstem resulting from PD. This will provide new insights to advance personalised treatment of PD patients and open new research avenues supporting prevention, diagnosis and management of co-morbidities in PD patients. Using models of mental comorbidities of PD, AND-PD will investigate functional changes in brainstem nuclei and establish the link with the anxiety phenotype. Findings will be used to inform pre-clinical (rodent, non-human primate and biobank samples) and clinical research (fMRI and PET imaging, behavioural analysis, retrospective cohort analysis) to identify and correlate causalities between dysfunctional neurocircuitry and co-morbid anxiety of PD. To prove causality, AND-PD will i) analyse anxiety in neurotoxin and genetic models of PD; ii) assess the physiological impact and behavioural effects of interventions that selectively reproduce the damage caused by PD in the brainstem; and iii) determine the ability of RNA based approaches to counteract anxiety associated with PD. To demonstrate the link in human patients, AND-PD will analyse patient databases and correlate measures of anxiety with: 1) signs of neuropathology in PD brain samples’ brainstem and 2) clinical and functional biomarkers of dysfunctional neurotransmission through brainstem imaging in patients. AND-PD beneficiaries’ experience in translational research will help ‘bridge the gap’ between preclinical and clinical experiments and help identify new anatomical targets and markers (molecular, functional and pathological,) to support better diagnosis, management and treatment of co-morbidities in PD patients.