Alpha synuclein has a key role in the pathogenesis of Parkinson’s disease (PD), Dementia with Lewy Bodies (LBD) and Multiple System Atrophy (MSA). Immunotherapies aiming at neutralising toxic αSyn species are being investigated in the clinic as potential disease modifying therapies for PD and other synucleinopathies. In this study, the effects of active immunisation against αSyn with the UB-312 vaccine were investigated in the Thy1SNCA/15 mouse model of PD. Young transgenic and wild-type mice received an immunisation regimen over a period of 6 weeks, then observed for an additional 9 weeks. Behavioural assessment was conducted before immunisation and at 15 weeks after the first dose. UB-312 immunisation prevented the development of motor impairment in the wire test and challenging beam test, which was associated with reduced levels of αSyn oligomers in the cerebral cortex, hippocampus and striatum of Thy1SNCA/15 mice. UB-312 immunotherapy resulted in a significant reduction of theαSyn load in the colon, accompanied by a reduction in enteric glial cell reactivity in the colonic ganglia. Our results demonstrate that immunisation with UB-312 prevents functional deficits and both central and peripheral pathology in Thy1SNCA/15 mice.

α 突触核蛋白在帕金森病 (PD)、路易体痴呆 (LBD) 和多系统萎缩 (MSA) 的发病机制中起关键作用。临床上正在研究旨在中和有毒 αSyn 物种的免疫疗法，作为 PD 和其他突触核蛋白病的潜在疾病修饰疗法。在这项研究中，在 Thy1SNCA/15 PD 小鼠模型中研究了 UB-312 疫苗对 αSyn 的主动免疫效果。年轻的转基因和野生型小鼠在 6 周内接受免疫方案，然后再观察 9 周。在免疫前和第一次接种后 15 周进行行为评估。UB-312 免疫预防了电线测试和挑战性光束测试中运动障碍的发展，这与 Thy1SNCA/15 小鼠大脑皮层、海马和纹状体中 αSyn 寡聚体水平降低有关。UB-312 免疫疗法导致结肠中的 αSyn 负荷显着降低，伴随着结肠神经节中肠神经胶质细胞反应性的降低。我们的结果表明，用 UB-312 免疫可预防 Thy1SNCA/15 小鼠的功能缺陷以及中枢和外周病变。