https://search.dev.ndltd.org/etd/aus-cath/oai:openresearch-repository.anu.edu.au:1885/733714465
type: CreativeWork
name: Targeted Gene Therapy Approaches for Huntington's Disease: Advancing Treatment through Bioengineered Self-Assembling Peptide Hydrogels and BDNF-Encoded Adeno-Associated Viruses, Applied In Vitro and In Vivo
description: An aging global population's demographic and epidemiological evolution has considerably affected healthcare accessibility and cost. This phenomenon is associated with progressive age-related pathologies such as neurodegenerative disorders. Also, CNS incapacity to regenerate is an obstacle to efficiently treating neurodegenerative diseases. Huntington's disease (HD) is recognized as a fatal neurodegenerative disorder caused by an unstable expansion of a single polyglutamine repeat in the huntingtin protein. It mainly enhances the loss of striatal neurons and primary cortical neurons within the forebrain. Gene therapy has provided promising targeted therapeutic strategies to treat various neurodegenerative disorders such as HD, where the genomic DNA of a cell can be rewritten, reengineered, and manipulated to change its fate controllably. This therapeutic alternative controls genetic or epigenetic disturbances, bringing promising outcomes compared with pharmacotherapy or invasive protein delivery. BDNF is a crucial regulator of synaptic and structural plasticity, higher cognitive functions, and survival of neuronal cells within the CNS. As evidenced by research, the BDNF plays a crucial role in protecting endangered striatal neurons and primary cortical neurons from cell death in the HD brain. However, several hurdles, such as short half-life, limited diffusion and cross over the blood-brain barrier, and poor pharmacokinetics, have hindered the trophic factors' progress towards therapeutic intervention. Viral gene delivery tools have emerged as alternative protein delivery strategies to surmount these issues. Despite various successes, the stimulating potential of viral gene therapy has yet to be fully realized, with multiple clinical trials failing to deliver optimum therapeutic results. Reasons include neutralization via the host immune system and resultant poor or inconsistent transduction efficiencies, off-target toxicities, and virion dissemination. Biomaterials …
abstract: An aging global population's demographic and epidemiological evolution has considerably affected healthcare accessibility and cost. This phenomenon is associated with progressive age-related pathologies such as neurodegenerative disorders. Also, CNS incapacity to regenerate is an obstacle to efficiently treating neurodegenerative diseases. Huntington's disease (HD) is recognized as a fatal neurodegenerative disorder caused by an unstable expansion of a single polyglutamine repeat in the huntingtin protein. It mainly enhances the loss of striatal neurons and primary cortical neurons within the forebrain. Gene therapy has provided promising targeted therapeutic strategies to treat various neurodegenerative disorders such as HD, where the genomic DNA of a cell can be rewritten, reengineered, and manipulated to change its fate controllably. This therapeutic alternative controls genetic or epigenetic disturbances, bringing promising outcomes compared with pharmacotherapy or invasive protein delivery. BDNF is a crucial regulator of synaptic and structural plasticity, higher cognitive functions, and survival of neuronal cells within the CNS. As evidenced by research, the BDNF plays a crucial role in protecting endangered striatal neurons and primary cortical neurons from cell death in the HD brain. However, several hurdles, such as short half-life, limited diffusion and cross over the blood-brain barrier, and poor pharmacokinetics, have hindered the trophic factors' progress towards therapeutic intervention. Viral gene delivery tools have emerged as alternative protein delivery strategies to surmount these issues. Despite various successes, the stimulating potential of viral gene therapy has yet to be fully realized, with multiple clinical trials failing to deliver optimum therapeutic results. Reasons include neutralization via the host immune system and resultant poor or inconsistent transduction efficiencies, off-target toxicities, and virion dissemination. Biomaterials …
author: Soltani Dehnavi, Shiva
language: en_AU
date published: 2024
date modified: 2026-07-24T01:07:14Z
provider: Australian Catholic University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Australian Catholic University

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property ID: Handle
value: https://hdl.handle.net/1885/733714465