TY - JOUR
T1 - Gene therapy for neurological disorders
T2 - Progress and prospects
AU - Deverman, Benjamin E.
AU - Ravina, Bernard M.
AU - Bankiewicz, Krystof S.
AU - Paul, Steven M.
AU - Sah, Dinah W.Y.
N1 - Funding Information:
The authors thank their colleagues at Voyager Therapeutics for numerous discussions on adeno-associated viral (AAV) gene therapy for central nervous system (CNS) disorders and the Parkinson disease team and P. Larson for their work on the delivery of AAV2–aromatic-l-amino-acid decarboxylase (AADC) gene therapy in patients with Parkinson disease with intraparenchymal brain administration. The authors also thank E. Smith, W. Yen and M. Lawrence for assistance with the figures, tables and text, respectively. B.E.D. was supported by the Beckman Institute for the CLARITY, Optogenetics and Vector Engineering Research Center (CLOVER) at the California Institute of Technology, the Friedreich’s Ataxia Research Alliance (FARA) and FARA Australasia and the CHDI Foundation and is currently supported by the Stanley Center for Psychiatric Research at Broad Institute. K.S.B. was supported by the Michael J. Fox Foundation. B.M.R., S.M.P. and D.W.Y.S. are currently employees of Voyager Therapeutics, a CNS gene therapy company working on AAV vectors for the treatment of severe neurological diseases.
Publisher Copyright:
©2018 Spri nger Nature Li mited. All ri ghts reserved.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Adeno-associated viral (AAV) vectors are a rapidly emerging gene therapy platform for the treatment of neurological diseases. In preclinical studies, transgenes encoding therapeutic proteins, microRNAs, antibodies or gene-editing machinery have been successfully delivered to the central nervous system with natural or engineered viral capsids via various routes of administration. Importantly, initial clinical studies have demonstrated encouraging safety and efficacy in diseases such as Parkinson disease and spinal muscular atrophy, as well as durability of transgene expression. Here, we discuss key considerations and challenges in the future design and development of therapeutic AAV vectors, highlighting the most promising targets and recent clinical advances.
AB - Adeno-associated viral (AAV) vectors are a rapidly emerging gene therapy platform for the treatment of neurological diseases. In preclinical studies, transgenes encoding therapeutic proteins, microRNAs, antibodies or gene-editing machinery have been successfully delivered to the central nervous system with natural or engineered viral capsids via various routes of administration. Importantly, initial clinical studies have demonstrated encouraging safety and efficacy in diseases such as Parkinson disease and spinal muscular atrophy, as well as durability of transgene expression. Here, we discuss key considerations and challenges in the future design and development of therapeutic AAV vectors, highlighting the most promising targets and recent clinical advances.
UR - http://www.scopus.com/inward/record.url?scp=85053084107&partnerID=8YFLogxK
U2 - 10.1038/nrd.2018.110
DO - 10.1038/nrd.2018.110
M3 - Review article
C2 - 30093643
AN - SCOPUS:85053084107
SN - 1474-1776
VL - 17
SP - 641
EP - 659
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 9
ER -