Morris, Gareth;
Schorge, Stephanie;
(2022)
Gene Therapy for Neurological Disease: State of the Art and Opportunities for Next-generation Approaches.
Neuroscience
, 490
pp. 309-314.
10.1016/j.neuroscience.2022.03.010.
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Abstract
Gene therapy for rare monogenetic neurological disorders is reaching clinics and offering hope to families affected by these diseases. There is also potential for gene therapy to offer new and effective treatments for common, non-genetic disorders. Treatments for Parkinson's Disease are in clinical trials, and treatments for refractory epilepsies are due to enter first-in-human clinical trials in 2022. Gene therapies for these disorders are based on delivering genes that address the mechanism of the disease, not repairing a mutated gene. Similar 'mechanistic' gene therapies could offer treatments to a wide range of neurological and neuropsychiatric diseases where there is a known mechanism that could be restored using gene therapy. However, the permanent nature of most gene therapies is a serious drawback for translation of gene therapies to a wide-range of diseases because it could present risk of irreversible adverse effects. Several lines of research are aimed at developing gene therapy approaches that allow for the treatment to be turned on and off, including: using proteins activated by exogenous ligands, and promoters turned on by activators. We review these approaches and propose an overall de-risking strategy for gene therapy for common neurological and psychiatric diseases. This approach is based on using a temporary mRNA-based treatment to initially assess efficacy and safety of the planned manipulation, and only following with permanent, virally-delivered treatment if the approach appears safe and effective.
| Type: | Article |
|---|---|
| Title: | Gene Therapy for Neurological Disease: State of the Art and Opportunities for Next-generation Approaches |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuroscience.2022.03.010 |
| Publisher version: | https://doi.org/10.1016/j.neuroscience.2022.03.010 |
| Language: | English |
| Additional information: | © 2022 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | epilepsy, gene therapy, genetic therapy, inducible promoters, microRNA |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148888 |
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