VectorY presents new pre-clinical data at the European Network for the Cure of ALS (ENCALS)
- Category: DNA RNA and Cells
- Published on Friday, 03 June 2022 15:38
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‘VecTabs’ developed using VectorY’s proprietary platform show positive effect on key drivers of ALS pathology
AMSTERDAM, The Netherlands I June 02, 2022 I VectorY, a biotech company focusing on the development of innovative gene therapy approaches for the treatment of neurodegenerative and muscular disorders through vectorized antibodies, today announced new data at the 2022 ENCALS meeting in Edinburgh.
The poster, which was presented on 1 June in McEwan Hall, d114, was titled “Reduction of oxidized phospholipids or misfolded protein aggregates by AAV-VecTabs in ALS pre-clinical models” (Sogorb-Gonzalez, M. et al). The new data demonstrate the therapeutic potential and versatility of VectorY’s VecTab platform technology, enabling development of secreted or intracellular antibody fragments that are AAV-vectorized and delivered to neurons and/or astrocytes, in vitro and in vivo.
TAR-DNA binding protein-43 (TDP-43) is necessary for the correct processing and transport of multiple mRNA’s that are essential for neuronal survival. Cytoplasmic mis-localized, misfolded or aggregated TDP-43 has been implicated in the pathogenesis of >97% of ALS patients. VectorY has confirmed that iPS-derived ALS motor neurons exhibit TDP-43 pathology. The Company has developed a library of single-chain variable fragments (scFv), named ‘VecTabs’, which are designed to exclusively bind to the misfolded, toxic TDP-43, while leaving the native TDP-43 functional. Today’s new data show that TDP-43-targeting intracellular VecTabs can effectively clear (large) TDP-43 aggregates from U2OS cells. In addition, iPS-derived ALS motor neurons were efficiently transduced with AAV to express TDP-43 VecTabs in a dose-dependent manner.
TDP-43 pathology and mitochondrial dysfunction are closely linked to formation of oxidized phospholipid (oxPL) species, which are highly toxic to motor neurons. Recent in vivo and ex vivo data indicate a pivotal role for oxPL in axonal damage and motor neuron death in ALS.
VectorY has developed AAV-expressed secreted VecTabs that specifically bind and neutralize oxPL, thereby protecting iPS-derived motor neurons from oxPL-mediated cell death. The biodistribution and expression of VecTabs in the central nervous system were investigated in mice and pigs. The results presented today demonstrated transduction of the target spinal cord and cortical motor neurons and expression of the therapeutic scFv antibodies. Multiple humanized and optimized constructs were generated, leading to the selection of VTx-001 and VTx-002 for further development in ALS.
Notes to Editors
VectorY combines the therapeutic potential of antibodies and gene therapy to develop long-lasting therapeutic solutions for neurodegenerative and -muscular diseases with high unmet medical need. Founded in October 2020 and based in the Amsterdam Science Park, VectorY is a fully integrated gene therapy company focused on the development of innovative therapeutics based on a novel AAV gene therapy platform, antibody-based targeted protein degradation technologies and proprietary manufacturing technology. While focusing initially on neurodegenerative and -muscular diseases, VectorY's synergistic technologies may be applied across a wide range of indications. VectorY’s manufacturing capabilities will include a state-of-the-art multi-product GMP facility in the Netherlands.
For more information, see www.vectorytx.com.