In the last two decades, gene therapy has made considerable achievements, particularly in the field of neurological diseases. Numerous proofs of concepts were made in animal models of genetic diseases and translational steps on large animals allowed phase I/II clinical trials for several severe neurodegenerative conditions. This concerned genetic (particularly lysosomal diseases) but also complex multifactorial disorders (Parkinson and Alzheimer’s diseases).
We improved our knowledge and identified critical issues thanks to first steps in clinical trials performed in humans. Further developments in gene therapy would allow the progression and optimization of future applications regarding vector tools, therapeutic constructs, delivery systems, design of preclinical evaluation and clinical trials.
The aim of this Research Topic is to present the state of the art of gene therapy for neurological diseases from a clinical perspective, and address most key aspects representing the current focus of research of the international scientific community. This will comprise
• The efficacy of gene therapy tools such as viral vectors, serotypes and therapeutic cassettes, the delivery systems manufacturing and quality control.
• Therapeutic strategies such as
- Gene replacement, silencing or editing in monogenic diseases;
- Targeting central pathways implicated in complex disease mechanisms (neurodegeneration, consequences of traumatic injury, chronic pain).
• The main limitations and concerns of gene therapy such as
- The immunogenicity especially how to anticipate potential risk, accurately evaluate clinical consequences, design preventive strategies and allow re-administration;
- The toxicity of the effective dose which can induce expression and potential silencing;
- Target patient population and clinical trial design (small size, efficacy endpoints, dose escalation…);
- Ethical and societal concerns as regards market size (very rare diseases, large size populations), cost and reimbursement.
"Topic Editor Dr Nathalie Cartier is the founder of BrainVectis that develops gene therapy treatments targeting the central nervous system. Dr Nicole Deglon declares no competing interests with regards to the Research Topic.
In the last two decades, gene therapy has made considerable achievements, particularly in the field of neurological diseases. Numerous proofs of concepts were made in animal models of genetic diseases and translational steps on large animals allowed phase I/II clinical trials for several severe neurodegenerative conditions. This concerned genetic (particularly lysosomal diseases) but also complex multifactorial disorders (Parkinson and Alzheimer’s diseases).
We improved our knowledge and identified critical issues thanks to first steps in clinical trials performed in humans. Further developments in gene therapy would allow the progression and optimization of future applications regarding vector tools, therapeutic constructs, delivery systems, design of preclinical evaluation and clinical trials.
The aim of this Research Topic is to present the state of the art of gene therapy for neurological diseases from a clinical perspective, and address most key aspects representing the current focus of research of the international scientific community. This will comprise
• The efficacy of gene therapy tools such as viral vectors, serotypes and therapeutic cassettes, the delivery systems manufacturing and quality control.
• Therapeutic strategies such as
- Gene replacement, silencing or editing in monogenic diseases;
- Targeting central pathways implicated in complex disease mechanisms (neurodegeneration, consequences of traumatic injury, chronic pain).
• The main limitations and concerns of gene therapy such as
- The immunogenicity especially how to anticipate potential risk, accurately evaluate clinical consequences, design preventive strategies and allow re-administration;
- The toxicity of the effective dose which can induce expression and potential silencing;
- Target patient population and clinical trial design (small size, efficacy endpoints, dose escalation…);
- Ethical and societal concerns as regards market size (very rare diseases, large size populations), cost and reimbursement.
"Topic Editor Dr Nathalie Cartier is the founder of BrainVectis that develops gene therapy treatments targeting the central nervous system. Dr Nicole Deglon declares no competing interests with regards to the Research Topic.