Recent progress and considerations for AAV gene therapies targeting the central nervous system

Erik Allen Lykken, Charles Shyng, Reginald James Edwards, Alejandra Rozenberg, Steven James Gray

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations


Background: Neurodevelopmental disorders, as a class of diseases, have been particularly difficult to treat even when the underlying cause(s), such as genetic alterations, are understood. What treatments do exist are generally not curative and instead seek to improve quality of life for affected individuals. The advent of gene therapy via gene replacement offers the potential for transformative therapies to slow or even stop disease progression for current patients and perhaps minimize or prevent the appearance of symptoms in future patients. Main body: This review focuses on adeno-associated virus (AAV) gene therapies for diseases of the central nervous system. An overview of advances in AAV vector design for therapy is provided, along with a description of current strategies to develop AAV vectors with tailored tropism. Next, progress towards treatment of neurodegenerative diseases is presented at both the pre-clinical and clinical stages, focusing on a few select diseases to highlight broad categories of therapeutic parameters. Special considerations for more challenging cases are then discussed in addition to the immunological aspects of gene therapy. Conclusion: With the promising clinical trial results that have been observed for the latest AAV gene therapies and continued pre-clinical successes, the question is no longer whether a therapy can be developed for certain neurodevelopmental disorders, but rather, how quickly.

Original languageEnglish (US)
Article number16
JournalJournal of neurodevelopmental disorders
Issue number1
StatePublished - May 18 2018


  • AAV9
  • Adeno-associated virus
  • Cellular immunity
  • Central nervous system
  • Clinical trial
  • Gene therapy
  • Neutralizing antibody

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cognitive Neuroscience


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