Targeted delivery to putamen via MRI-guided surgery: Nonhuman primate versus Göttingen minipig®

ASGCT 2025 -- Recent advances in clinical approaches delivering targeted gene or cell therapies to the brain using MRI-guidance have necessitated in vivo safety studies applying the similar procedures used in the clinical studies. While the standard preclinical animal model, to date, has been the nonhuman primate (NHP), the Göttingen minipig has emerged as an important human-relevant preclinical model for brain and central nervous system (CNS) targeted gene or cell therapies. The minipig is a more translatable model than rodents and validation could allow for the minipig to be an alternative to the use of NHPs. The NHP and minipig brain are similar to the human brain developmentally, anatomically and neurochemically, and represent valuable models for therapies intended to target the CNS. Neurodegeneration in the putamen, as indicated in Parkinson’s and Huntington’s disease, requires precise treatment for gene replacement or disease reversibility. We demonstrated the feasibility, tolerability and challenges of direct targeting of the putamen using MRI-guided SmartFlow® cannula-based infusion and the ClearPoint® Pre-clinical Orchestra™ head fixation frame in NHPs and Göttingen minipigs.