Gene Therapy for Neurodevelopmental Disorders

Abstract

Abstract Neurodevelopmental disorders (NDDs) are a heterogeneous group of devastating conditions characterised by impairments of the central nervous system early during course of development and maturation. Although common NDDs tend to have complex aetiology, other major NDDs are inherited disorders with a known single‐gene or chromosomal abnormality. Effective treatments are rare for these diseases. The most critical challenges in therapeutic development are the broad, complex neuropathology and circumventing the blood–brain barrier. Gene therapy has been a promising approach for treating NDDs, especially monogenic disorders. With recent progress in understanding the disease mechanisms, and improvements to gene delivery vectors and strategies, the clinical potential of gene therapy for NDDs is being realised. This is particularly true for the neuropathic lysosomal storage diseases, in which multiple promising vector administration approaches are under development. Key Concepts: Gene therapy provides therapeutics by delivery of targeted genes. Monogenic NDDs are good candidates for gene therapies that target the root causes. Neuropathology of NDDs is usually broad or global in the CNS. The blood–brain barrier poses a major challenge for CNS gene delivery. Adeno‐associated virus serotype 9 vector has the ability to cross the blood–brain barrier.