Evaluation of an Adoptive Cellular Therapy-Based Vaccine in a Transgenic Mouse Model of α-synucleinopathy

Abstract

Aggregated α-synuclein, a major constituent of Lewy bodies plays a crucial role in the pathogenesis of α-synucleinopathies (SPs) such as Parkinson's disease (PD). PD is affected by the innate and adaptive arms of the immune system, and recently both active and passive immunotherapies targeted against α-synuclein (α-syn) are being developed and show promise as novel treatment strategies for such diseases. Specifically, dendritic cell-based vaccines have shown to be an effective treatment for SPs. Here, we report on the development of adoptive cellular therapy (ACT) for SP and demonstrate that adoptive transfer of pre-activated T-cells generated from immunized mice can improve survival and behavior, reduce brain microstructural impairment via magnetic resonance imaging (MRI), and decrease α-synuclein pathology burden in a peripherally induced preclinical SP model (M83) when administered prior to disease onset. This study provides evidence for ACT as a candidate immunotherapy for other forms of SPs.

Neuroanatomical and cognitive biomarkers of alpha‐synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms

“…Recent studies have shown the potential of neuroimaging techniques for examining brain-correlates of aSyn toxicity in animal models (Chu et al, 2020(Chu et al, , 2022Lackie et al, 2022); namely, Chu et al ( 2020) provides preliminary evidence for diffusion and functional MRI markers linked to the progression of aSyn pathology.…”

“…Recent studies have shown the potential of neuroimaging techniques for examining brain‐correlates of aSyn toxicity in animal models (Chu et al, 2020, 2022; Lackie et al, 2022); namely, Chu et al (2020) provides preliminary evidence for diffusion and functional MRI markers linked to the progression of aSyn pathology. In terms of structural MRI, a common modality acquired in clinical research to examine the brain morphology and signs of atrophy and neurodegeneration in human patients, our group has examined neuroanatomy using structural MRI in the M83 homozygous mouse model, which however does not provide information on seed‐initiation of pathology as PFF‐injected mice (Lackie et al, 2022).…”