Progress and Challenges in Clinical AAV Gene Therapy for Neurological and Neuromuscular Disorders

The field of gene therapy is growing at a rapid pace. The discovery and modification of adeno-associated viruses (AAV) as gene therapy vectors has allowed for the development of novel treatments for neurological and neuromuscular disorders. AAV based gene therapy techniques can be utilized to add, replace, or modify genes and their expression in patients, thus providing a potential beneficial therapeutic effect. In many cases, gene therapy has the promising power to change the natural course of debilitating and fatal diseases and give patients a new outcome on life. This mini review will give a brief overview of the AAV gene therapy field, highlighting FDA approved gene therapies and selected current in-clinic AAV-mediated therapeutics for neurological and neuromuscular diseases for which interim data are available. These therapies and the ongoing clinical trials are currently laying the groundwork for future gene therapy strategies and clinical trial design. Ultimately, they will inform the field on promises and limitations that still need to be overcome.

Keywords: Gene Therapy; AAV; Neuromuscular Disorders

Abbreviations: AAV- Adeno-associated virus; RAAV- Recombinant adeno-associated virus; ITRs- Inverted terminal repeats. FDA-Food and Drug Administration; CNS-Central nervous system; IV- Intravenous; NCL-Neuronal ceroid lipofuscinosis; CSF- Cerebrospinal fluid; IT- Intrathecal; PDParkinson’s Disease; ALS- Amyotrophic Lateral Sclerosis; DMD- Duchenne Muscular Dystrophy