Systemic Safety of a Recombinant AAV8 Vector for Human Cocaine Hydrolase Gene Therapy: A Good Laboratory Practice Preclinical Study in Mice.

ABSTRACT: Cocaine addiction continues to impose major burdens on affected individuals and broader society but is highly resistant to medical treatment or psychotherapy. This study was undertaken with the goal of Food and Drug Administration (FDA) permission for a first-in-human clinical trial of a gene therapy for treatment-seeking cocaine users to become and remain abstinent. The approach was based on intravenous administration of AAV8-hCocH, an adeno-associated viral vector encoding a modified plasma enzyme that metabolizes cocaine into harmless by-products. To assess systemic safety, we conducted "Good Laboratory Practice" (GLP) studies in cocaine-experienced and cocaine-naive mice at doses of 5E12 and 5E13 vector genomes/kg. Results showed total lack of viral vector-related adverse effects in al

SUBMITTER: Chen VP 

PROVIDER: S-EPMC6985763 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature