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Papers: 7 Nov 2020 - 13 Nov 2020

2020 Nov 09

Hum Gene Ther

The challenge of gene therapy for neurological diseases: strategies and tools to achieve efficient delivery to the central nervous system.


Piguet F, de Saint Denis T, Audouard E, Beccaria K, Arthur A, Wurtz G, Schatz R, Alves S, Sevin C, Zerah M, Cartier N
Hum Gene Ther. 2020 Nov 09.
PMID: 33167739.


For more than ten years, gene therapy for neurological diseases has experienced intensive research growth and more recently therapeutic interventions for multiple indicationsBeneficial results in several phase 1/2 clinical studies, together with improved vector technology have advanced gene therapy for the central nervous system (CNS) in a new era of development. While most initial strategies have focused on orphan genetic diseases, such as lysosomal storage diseases, more complex and widespread conditions like Alzheimer's disease, Parkinson's disease, epilepsy or chronic pain are increasingly targeted for gene therapy. Increasing numbers of applications and patients to be treated will require improving and simplifying gene therapy protocols to make them accessible to the largest number of affected people. While vectors and manufacturing are a major field of academic research and industrial development, there is a growing need to improve, standardize and simplify delivery methods. Delivery is the major issue for CNS therapies in general, and particularly for gene therapy. The blood brain barrier restricts the passage of vectors; and strategies to bypass this obstacle are a central focus of research. Here, we present the different ways that can be used to deliver gene therapy products to the CNS. We focus on results obtained in large animals that have allowed the transfer of protocols to human patients and have resulted in the generation of clinical data. We discuss the different routes of administration, their advantages and their limitations. We describe techniques, equipment and protocols and how they should be selected for safe delivery and improved efficiency for the next generation of gene therapy trials for CNS diseases.