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  • Millennium Review
  • Published:

Gene therapy in the CNS

Abstract

Gene therapy for neurological disorder is currently an experimental concept. The goals for clinical utilization are the relief of symptoms, slowing of disease progression, and correction of genetic abnormalities. Experimental studies are realizing these goals in the development of gene therapies in animal models. Discoveries of the molecular basis of neurological disease and advances in gene transfer systems have allowed focal and global delivery of therapeutic genes for a wide variety of CNS disorders. Limitations are still apparent, such as stability and regulation of transgene expression, and safety of both vector and expressed transgene. In addition, the brain adds several challenges not seen in peripheral gene therapy paradigms, such as post-mitotic cells, heterogeneity of cell types and circuits, and limited access. Moreover, it is likely that several modes of gene delivery will be necessary for successful gene therapies of the CNS. Collaborative efforts between clinicians and basic researchers will likely yield effective gene therapy in the CNS.

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Acknowledgements

We thank Ms Suzanne McDavitt for skilled preparation of this manuscript. LCC is a recipient of a fellowship from the McLean Hospital Clinical Neuroscience Training Grant (T32 MH 19905). Funding to XOB and JB was provided by NINDS grant NS24279 and NIMH grant R21MH60587, and to OI by McLean Hospital research funding and (P50) NS39793-01.

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Costantini, L., Bakowska, J., Breakefield, X. et al. Gene therapy in the CNS. Gene Ther 7, 93–109 (2000). https://doi.org/10.1038/sj.gt.3301119

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