Direct convective delivery of adeno-associated virus gene therapy for treatment of neurological disorders

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  • 1 Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio; and
  • 2 Department of Neurological Surgery, Bródno Hospital, Warsaw, Poland
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Molecular biological insights have led to a fundamental understanding of the underlying genomic mechanisms of nervous system disease. These findings have resulted in the identification of therapeutic genes that can be packaged in viral capsids for the treatment of a variety of neurological conditions, including neurodegenerative, metabolic, and enzyme deficiency disorders. Recent data have demonstrated that gene-carrying viral vectors (most often adeno-associated viruses) can be effectively distributed by convection-enhanced delivery (CED) in a safe, reliable, targeted, and homogeneous manner across the blood-brain barrier. Critically, these vectors can be monitored using real-time MRI of a co-infused surrogate tracer to accurately predict vector distribution and transgene expression at the perfused site. The unique properties of CED of adeno-associated virus vectors allow for cell-specific transgene manipulation of the infused anatomical site and/or widespread interconnected sites via antero- and/or retrograde transport. The authors review the convective properties of viral vectors, associated technology, and clinical applications.

ABBREVIATIONS AADC = aromatic l-amino acid decarboxylase; AAV = adeno-associated virus; BBB = blood-brain barrier; CED = convection-enhanced delivery; GAD = glutamic acid decarboxylase; GDNF = glial cell–derived neurotrophic factor; PD = Parkinson’s disease; STN = subthalamic nucleus.

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Contributor Notes

Correspondence Russell R. Lonser: The Ohio State University Wexner Medical Center, Ohio State University, Columbus, OH. russell.lonser@osumc.edu.

INCLUDE WHEN CITING Published online July 10, 2020; DOI: 10.3171/2020.4.JNS20701.

Disclosures Dr. Lonser: direct stock ownership in Brain Neurotherapy Bio, Inc. Dr. Bankiewicz: ownership in Voyager Therapy and Brain Neurotherapy Bio, Inc.

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