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Abstracts from the International Congress of Parkinson’s and Movement Disorders.

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Repeated Scanning Ultrasound in an Alpha-synuclein Preformed Fibril model

V. Purrer, K. Roffey, G. Richter-Stretton, J. Song, G. Leinenga, L. Chen, E. Albornoz Balmaceda, J. Götz (St Lucia, Australia)

Meeting: 2025 International Congress

Keywords: Alpha-synuclein, Experimental therapeutics, Parkinson’s

Category: Parkinson's Disease (Other)

Objective: To investigate the therapeutic potential of repeated scanning ultrasound (SUS)-mediated blood-brain barrier (BBB) opening in a mouse model of Parkinson’s disease (PD).

Background: PD is characterized by the misfolding and aggregation of alpha-synuclein (αSyn), leading to the formation of Lewy bodies and progressive dopaminergic neurodegeneration. Current treatments remain symptomatic and do not modify disease progression. Strategies targeting αSyn aggregation, including immunotherapies, are often limited by the BBB, which restricts the delivery of most therapeutic compounds. SUS, in combination with microbubbles (MBs), offers a non-invasive method to safely and transiently open the BBB, potentially promoting protein clearance or facilitating drug delivery. However, the direct effects of ultrasound on αSyn pathology and associated neuroinflammatory responses remain unclear.

Method: Four weeks after intracerebral injection of αSyn preformed fibrils (PFFs), adult wild-type mice underwent multiple SUS treatments, either with or without MB administration. At baseline and after SUS application, motor performances were assessed monthly using the Rotarod and balance beam test. Tissue was collected two months after the final SUS treatment for immunohistochemical analysis and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI).

Results: ΑSyn levels, neuroinflammatory response, protein clearance pathways, and motor function were evaluated to determine the impact of SUS on PD pathology. Further, MALDI-MSI was used to explore potential alterations in the dopaminergic system.

Conclusion: This study explores the potential of SUS as a non-pharmacological intervention for PD by examining its effects on αSyn aggregation and related pathological processes. Understanding these mechanisms may contribute to future therapeutic strategies, including the use of SUS for enhancing targeted drug delivery across the BBB.

To cite this abstract in AMA style:

V. Purrer, K. Roffey, G. Richter-Stretton, J. Song, G. Leinenga, L. Chen, E. Albornoz Balmaceda, J. Götz. Repeated Scanning Ultrasound in an Alpha-synuclein Preformed Fibril model [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/repeated-scanning-ultrasound-in-an-alpha-synuclein-preformed-fibril-model/. Accessed October 5, 2025.
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