Clinical gene therapy development for the central nervous system: Candidates and challenges for AAVs
Tiffany W Leong1, Arindam Pal1, Qi Cai2
1Department of Bioengineering, The University of Texas at Dallas, Richardson, TX 75080, USA.
Abstract:
Many diseases affecting the central nervous system (CNS) are deadly but less understood, leading to impaired mental and motor capabilities and poor patient prospects. Gene therapy is a promising therapeutic modality for correcting many genetic disorders, expanding in breadth and scope with further advances. This review summarizes the candidate CNS disorders for gene therapy, mechanisms of gene therapy, and recent clinical advances and limitations of gene therapy in CNS disorders. We highlight that improving delivery across CNS barriers, safety, monitoring techniques, and multiplexing therapies are predominant factors in advancing long-term outcomes from gene therapy.
Insights
Gene therapy offers hope for deadly central nervous system (CNS) diseases by correcting genetic disorders. Advances focus on improving delivery, safety, and monitoring for better long-term patient outcomes.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Central nervous system (CNS) diseases often have poor prognoses due to limited understanding and treatment options.
- Gene therapy presents a promising approach for addressing genetic disorders affecting the CNS.
- Recent advancements are expanding the scope and application of gene therapy for neurological conditions.
Purpose of the Study:
- To review candidate CNS disorders suitable for gene therapy.
- To elucidate the mechanisms underlying gene therapy for CNS applications.
- To summarize recent clinical progress and identify limitations in CNS gene therapy.
Main Methods:
- Literature review of gene therapy for CNS disorders.
- Analysis of current clinical trial data and research findings.
- Identification of key challenges and future directions in the field.
Main Results:
- Gene therapy is being explored for a range of debilitating CNS disorders.
- Successful gene therapy requires overcoming significant biological barriers, particularly CNS barriers.
- Ongoing research is refining delivery methods, safety protocols, and monitoring techniques.
Conclusions:
- Improving the delivery of gene therapies across the blood-brain barrier is crucial.
- Enhanced safety measures and reliable monitoring are essential for clinical success.
- Multiplexing therapeutic strategies may offer improved long-term outcomes for patients with CNS disorders.
