Details

Autor(en) / Beteiligte

• Schlichtmann, Benjamin W
• Palanisamy, Bharathi N
• Malovic, Emir
• Nethi, Susheel K
• Padhi, Piyush
• Hepker, Monica
• Wurtz, Joseph
• John, Manohar
• Ban, Bhupal
• Anantharam, Vellareddy
• Kanthasamy, Anumantha G
• Narasimhan, Balaji
• Mallapragada, Surya K

Titel

Aggregation-Inhibiting scFv-Based Therapies Protect Mice against AAV1/2-Induced A53T-α-Synuclein Overexpression

Ist Teil von

• Biomolecules (Basel, Switzerland), 2023-07, Vol.13 (8), p.1203

Ort / Verlag

Basel: MDPI AG

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• To date, there is no cure for Parkinson’s disease (PD). There is a pressing need for anti-neurodegenerative therapeutics that can slow or halt PD progression by targeting underlying disease mechanisms. Specifically, preventing the build-up of alpha-synuclein (αSyn) and its aggregated and mutated forms is a key therapeutic target. In this study, an adeno-associated viral vector loaded with the A53T gene mutation was used to induce rapid αSyn-associated PD pathogenesis in C57BL/6 mice. We tested the ability of a novel therapeutic, a single chain fragment variable (scFv) antibody with specificity only for pathologic forms of αSyn, to protect against αSyn-induced neurodegeneration, after unilateral viral vector injection in the substantia nigra. Additionally, polyanhydride nanoparticles, which provide sustained release of therapeutics with dose-sparing properties, were used as a delivery platform for the scFv. Through bi-weekly behavioral assessments and across multiple post-mortem immunochemical analyses, we found that the scFv-based therapies allowed the mice to recover motor activity and reduce overall αSyn expression in the substantia nigra. In summary, these novel scFv-based therapies, which are specific exclusively for pathological aggregates of αSyn, show early promise in blocking PD progression in a surrogate mouse PD model.