TY - JOUR
T1 - Recent progress and considerations for AAV gene therapies targeting the central nervous system
AU - Lykken, Erik Allen
AU - Shyng, Charles
AU - Edwards, Reginald James
AU - Rozenberg, Alejandra
AU - Gray, Steven James
N1 - Funding Information:
The authors acknowledge the support from Hannah’s Hope Fund, the University of Texas Southwestern Medical Center Department of Pediatrics, and NICHD grant T32HD040127.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/5/18
Y1 - 2018/5/18
N2 - Background: Neurodevelopmental disorders, as a class of diseases, have been particularly difficult to treat even when the underlying cause(s), such as genetic alterations, are understood. What treatments do exist are generally not curative and instead seek to improve quality of life for affected individuals. The advent of gene therapy via gene replacement offers the potential for transformative therapies to slow or even stop disease progression for current patients and perhaps minimize or prevent the appearance of symptoms in future patients. Main body: This review focuses on adeno-associated virus (AAV) gene therapies for diseases of the central nervous system. An overview of advances in AAV vector design for therapy is provided, along with a description of current strategies to develop AAV vectors with tailored tropism. Next, progress towards treatment of neurodegenerative diseases is presented at both the pre-clinical and clinical stages, focusing on a few select diseases to highlight broad categories of therapeutic parameters. Special considerations for more challenging cases are then discussed in addition to the immunological aspects of gene therapy. Conclusion: With the promising clinical trial results that have been observed for the latest AAV gene therapies and continued pre-clinical successes, the question is no longer whether a therapy can be developed for certain neurodevelopmental disorders, but rather, how quickly.
AB - Background: Neurodevelopmental disorders, as a class of diseases, have been particularly difficult to treat even when the underlying cause(s), such as genetic alterations, are understood. What treatments do exist are generally not curative and instead seek to improve quality of life for affected individuals. The advent of gene therapy via gene replacement offers the potential for transformative therapies to slow or even stop disease progression for current patients and perhaps minimize or prevent the appearance of symptoms in future patients. Main body: This review focuses on adeno-associated virus (AAV) gene therapies for diseases of the central nervous system. An overview of advances in AAV vector design for therapy is provided, along with a description of current strategies to develop AAV vectors with tailored tropism. Next, progress towards treatment of neurodegenerative diseases is presented at both the pre-clinical and clinical stages, focusing on a few select diseases to highlight broad categories of therapeutic parameters. Special considerations for more challenging cases are then discussed in addition to the immunological aspects of gene therapy. Conclusion: With the promising clinical trial results that have been observed for the latest AAV gene therapies and continued pre-clinical successes, the question is no longer whether a therapy can be developed for certain neurodevelopmental disorders, but rather, how quickly.
KW - AAV9
KW - Adeno-associated virus
KW - Cellular immunity
KW - Central nervous system
KW - Clinical trial
KW - Gene therapy
KW - Neutralizing antibody
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U2 - 10.1186/s11689-018-9234-0
DO - 10.1186/s11689-018-9234-0
M3 - Review article
C2 - 29776328
AN - SCOPUS:85047563233
SN - 1866-1947
VL - 10
JO - Journal of neurodevelopmental disorders
JF - Journal of neurodevelopmental disorders
IS - 1
M1 - 16
ER -