Principal Director Charles River Laboratories Laval, Quebec, Canada
Gene therapy, particularly utilizing AAV vectors, has emerged as a promising approach for treating various genetic disorders, including those affecting the central nervous system (CNS). However, the development of such therapies necessitates a comprehensive understanding of program design, including product-specific considerations regarding immunology, insertional mutagenesis, germ line transmission and laboratory assays, regulatory considerations, and expected and potential unexpected toxicology results during risk assessment. This talk will present a case study of an AAV program with CNS delivery for an orphan indication, offering insights into the overall program design, dose level selection, risk assessment, species selection, and biodistribution analysis. Special emphasis will be placed on toxicology endpoints such as neuropathology, clinical pathology, and nerve conduction velocity. The audience will be asked to address industry relevant aspects of AAV program with CNS delivery for an orphan indication during group discussions. Learning objectives: 1) understand and critically evaluate the multiple valid approaches for gene therapy development, 2) understand the toxicological concepts specific to gene therapy critical for risk assessment, and 3) understand the impact of regulatory feedback on the case-by-case approach to AAV development programs.
