Research Topic

Gene Therapy in the CNS – Progress and Prospects for Novel Therapies

About this Research Topic

Gene therapy for central nervous system (CNS) disorders holds a compelling potential for the development of novel therapies. It offers the potential of transformative and disease-modulating treatment opportunities, with long-lived therapeutic effect where current standard treatments are unsatisfying. Recent advances in the field have renewed the optimisms on the possibility to develop new innovative solutions.

Gene therapy encompasses the administration of recombinant nucleic acid, to adjust, repair, replace, add, or remove a targeted gene sequence involved in the disease. New administration technologies have expanded the possibilities allowing for gene silencing, down-regulation, removal, replacement or insertion. In diseases stemming from defective genes, this could involve the introduction of a healthy variant, e.g., as attempted in Canavan’s Disease, one of the first CNS diseases subjected to gene therapy. Gene-editing technologies, such as the CRISPR/Cas9 system allows genome manipulation, e.g., applied in to target genetic components of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In addition, specific targeting of cells or circuits can be obtained via disease-modifying gene transfer or via the introduction of genes encoding for proteins introducing de novo sensitivity to specific drugs or to light stimulation. This is the case for example, of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and other chemogenetics, as well as optogenetic approaches to control epileptiform activity in seizures.

To realize new CNS gene therapies, multiple challenges must be addressed, including the identification of a beneficial therapeutic target matching the disease complexity and progression, the development of efficient administration techniques and sustained treatment responses, identification of effective, safe, finely-targeted, and regulated delivery, and proof-of-concept on the overall superiority compared to current available treatments. Recent success to target genetically defined diseases such as the approval of Zolgensma for spinal muscular atrophy (SMA) in pediatric patients has catalyzed an increasing activity and creativity to overcome these hurdles.

This Research Topic aims to collect and provide an overview of the novel discoveries and technologies relevant to CNS diseases at the center of attention as gene therapy targets, in particular neurological (e.g. epilepsy and multiple system atrophies), neurodevelopmental (e.g., autism spectrum disorders), neuroimmunological (e.g., multiple sclerosis), neurodegenerative (e.g., Alzheimer’s, Parkinson’s, and Huntington’s disease), and neuromuscular disorders (e.g., spinal muscular atrophies and amyotrophic lateral sclerosis).

We welcome original research, reviews, and technological articles on progress and prospects for gene therapy in CNS disorders, potentially inspiring the development of novel treatment possibilities, focusing on:

• Obtaining an in-depth understanding of the biological aspects and underlying mechanisms involved in therapeutic gene transfer in the CNS, employing molecular technologies for in vitro, ex vivo and in vivo approaches;
• Application of gene-editing (e.g. CRISPR/Cas9), optogenetics, chemogenetics, and viral-vector-mediated gene transfer to target CNS diseases; findings of the most promising CNS disorder gene therapies and methods of administration focusing on new discoveries and future possibilities;
• Translational value for the trajectory towards clinical testing of tailored CNS disorders treatment, focusing on ex vivo and in vivo approaches, including various disease models


Guest Editor Casper R. Gøtzsche is a medical and scientific partner of UCB Nordic A/S. All other Guest Editors declare no competing interests with regards to the Research Topic subject



Keywords: Gene therapy, Gene editing, Central Nervous System, Disease modulation, Novel treatments


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Gene therapy for central nervous system (CNS) disorders holds a compelling potential for the development of novel therapies. It offers the potential of transformative and disease-modulating treatment opportunities, with long-lived therapeutic effect where current standard treatments are unsatisfying. Recent advances in the field have renewed the optimisms on the possibility to develop new innovative solutions.

Gene therapy encompasses the administration of recombinant nucleic acid, to adjust, repair, replace, add, or remove a targeted gene sequence involved in the disease. New administration technologies have expanded the possibilities allowing for gene silencing, down-regulation, removal, replacement or insertion. In diseases stemming from defective genes, this could involve the introduction of a healthy variant, e.g., as attempted in Canavan’s Disease, one of the first CNS diseases subjected to gene therapy. Gene-editing technologies, such as the CRISPR/Cas9 system allows genome manipulation, e.g., applied in to target genetic components of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In addition, specific targeting of cells or circuits can be obtained via disease-modifying gene transfer or via the introduction of genes encoding for proteins introducing de novo sensitivity to specific drugs or to light stimulation. This is the case for example, of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and other chemogenetics, as well as optogenetic approaches to control epileptiform activity in seizures.

To realize new CNS gene therapies, multiple challenges must be addressed, including the identification of a beneficial therapeutic target matching the disease complexity and progression, the development of efficient administration techniques and sustained treatment responses, identification of effective, safe, finely-targeted, and regulated delivery, and proof-of-concept on the overall superiority compared to current available treatments. Recent success to target genetically defined diseases such as the approval of Zolgensma for spinal muscular atrophy (SMA) in pediatric patients has catalyzed an increasing activity and creativity to overcome these hurdles.

This Research Topic aims to collect and provide an overview of the novel discoveries and technologies relevant to CNS diseases at the center of attention as gene therapy targets, in particular neurological (e.g. epilepsy and multiple system atrophies), neurodevelopmental (e.g., autism spectrum disorders), neuroimmunological (e.g., multiple sclerosis), neurodegenerative (e.g., Alzheimer’s, Parkinson’s, and Huntington’s disease), and neuromuscular disorders (e.g., spinal muscular atrophies and amyotrophic lateral sclerosis).

We welcome original research, reviews, and technological articles on progress and prospects for gene therapy in CNS disorders, potentially inspiring the development of novel treatment possibilities, focusing on:

• Obtaining an in-depth understanding of the biological aspects and underlying mechanisms involved in therapeutic gene transfer in the CNS, employing molecular technologies for in vitro, ex vivo and in vivo approaches;
• Application of gene-editing (e.g. CRISPR/Cas9), optogenetics, chemogenetics, and viral-vector-mediated gene transfer to target CNS diseases; findings of the most promising CNS disorder gene therapies and methods of administration focusing on new discoveries and future possibilities;
• Translational value for the trajectory towards clinical testing of tailored CNS disorders treatment, focusing on ex vivo and in vivo approaches, including various disease models


Guest Editor Casper R. Gøtzsche is a medical and scientific partner of UCB Nordic A/S. All other Guest Editors declare no competing interests with regards to the Research Topic subject



Keywords: Gene therapy, Gene editing, Central Nervous System, Disease modulation, Novel treatments


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

19 June 2020 Abstract
18 September 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

19 June 2020 Abstract
18 September 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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