BBB seminar: Krystof Bankiewicz
Convection enhanced delivery of nanoparticles and retroviral replicating vector into recurrent brain tumors under real-time MRI guidance
Department of Neurological Surgery, University of California San Francisco, CA, USA
Convection enhanced delivery (CED) is a promising approach for delivering therapeutics to the brain. It bypasses the blood brain barrier and permits volumetric coverage of targeted brain structures. Prior clinical trials that have utilized CED to administer therapeutics have produced sub-standard outcomes and technical limitations in the administration of the therapy are considered to be a significant contributing factor to these failures. We are performing several phase I safety studies that utilize an optimized delivery platform and magnetic resonance imaging (MRI) guidance to administer gene therapy and nanoparticles in patients with recurrent brain tumors and Parkinson’s disease.
To allow for precise intra-cerebral delivery of biologics for therapy of neurological disease we developed a skull-mounted aiming device (SmartFrame) and integrated software platform (ClearPoint) for interventional MRI guided placement of devices for real-time CED of therapeutics via a custom designed infusion cannula. Based on real-time MRI data, this system allows selection of brain targets, provides instructions for cannula insertion along a chosen trajectory, and permits visual monitoring of infusions.
Intra-tumoral infusions of investigational nanoparticles (CPT-11) or retroviral replicating vector were effectively targeted and monitored with real-time intra-operative MRI methods. Intra-operative monitoring allows for correction of the infusion process when the desired coverage is not being achieved. This ability to adapt in real-time enables improved tumor coverage and minimizes the potential for extra-tumoral administration of the vector. Our up to date clinical data will be presented.
Chairperson: Hrvoje Miletic, Department of Biomedicine