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Your search keyword '"De Angelis, Rolando"' showing total 10 results
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10 results on '"De Angelis, Rolando"'

1. Vector genome loss and epigenetic modifications mediate decline in transgene expression of AAV5 vectors produced in mammalian and insect cells

Author

Handyside, Britta, Ismail, Ashrafali Mohamed, Zhang, Lening, Yates, Bridget, Xie, Lin, Sihn, Choong-Ryoul, Murphy, Ryan, Bouwman, Taren, Kim, Chan Kyu, De Angelis, Rolando, Karim, Omair A., McIntosh, Nicole L., Doss, Michael Xavier, Shroff, Shilpa, Pungor, Erno, Bhat, Vikas S., Bullens, Sherry, Bunting, Stuart, and Fong, Sylvia

Published
2022
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2. Intracerebroventricular administration of a modified hexosaminidase ameliorates late-stage neurodegeneration in a GM2 mouse model.

Author

Lopez, Manuel E., Wendt, Daniel, Lawrence, Roger, Gong, Kerui, Ong, Hoonsan, Yip, Bryan, Chen, Joseph, Mangini, Linley, Handyside, Britta, Giaramita, Alexander, Lamichhane, Aashish, Lo, Melanie, Agrawal, Vishal, Van Vleet, Jeremy, Abolhesn, Amanda, Felix, Jessica B., Villalpando, Isaac, Bhat, Vikas, De Angelis, Rolando, and Ru, Yuanbin

Subjects
ENZYME replacement therapy, ENZYME stability, NEURODEGENERATION, LABORATORY mice, HEXOSAMINIDASE
Abstract

The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease. Enzyme replacement therapy was administered by repeat intracerebroventricular injections in Sandhoff disease model mice with dosing beginning before and after signs of neurodegeneration. As previously observed, HexA effectively increased the lifespan of Sandhoff disease mice by 3.5-fold only when treatment was started before onset of neurodegeneration. In contrast, HexD3 halted motor decline and ameliorated late-stage disease severity even when dosing began late, after neurodegeneration onset. Additionally, HexD3 had advantages over HexA in enzyme stability, distribution potential, and homodimer activity. Overall, our data indicate that advanced therapeutics may widen the treatment window for neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Published
2025
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