Gene therapy and neurodevelopmental disorders

With a number of recent clinical successes, gene therapy is quickly becoming a realistic treatment option for neurological disorders. Advancements in global central nervous system (CNS) gene delivery, in particular, have accelerated to the point that treatments for neurological disorders such as lysosomal storage diseases seem within reach. Other neurodevelopmental disorders, such as Rett Syndrome, Fragile X, and autism still face significant obstacles to overcome before a viable human gene therapy can be considered. This review focuses on the most common CNS gene delivery vehicle, adeno-associated virus (AAV), and the current state of AAV vector design and delivery for CNS gene therapy. Relevant examples of gene therapy studies for neurodevelopmental disorders, as well as outstanding challenges, are discussed.This article is part of the Special Issue entitled ‘Neurodevelopmental Disorders’.

► New developments in AAV vector design are permitting global CNS gene delivery.
► Expression can be modulated by optimizing both the capsid and genome of vectors.
► Lysosomal storage diseases represent an immediate target for gene therapy.
► Disorders such as Rett and Angelman syndrome face considerable challenges.