Jerneja Stare, PhD and Erik Larson, PhD
Advances in MRI Technology
A window for innovative gene therapies for CNS
Recent advances in neurosurgical technologies have allowed for significant improvements in targeted drug delivery in preclinical and clinical settings. One recent breakthrough has been the real-time visualization of gene therapy delivery into the brain for the treatment of central nervous system (CNS) disorders.
Off target central nervous system side effects such as seizures, headaches, fatigue, or tremors are some of the leading causes of drug development failure and these convection-enhanced delivery (CED) techniques, developed to facilitate targeted delivery of pharmaceuticals to the brain, have the potential to minimize off-target side effects. The CED procedure involves a minimally invasive surgical exposure of the brain—one which our lab is using to provide a window into a targeted area in the brain that is involved in the pathology of a target disease.
Going Past the Blood-Brain-Barrier
Using the novel ClearPoint® System, we’re taking traditional stereotaxic surgical procedures coupled with modern neurosurgical techniques to bring real-time, intraoperative MRI (iMRI)-guided test item delivery to the brain. Real-time iMRI-guided targeting allows for precise, predictable, and reproducible delivery into brain structures with submillimetric (< 0.5 mm) accuracy. By coupling the test item with a contrast agent, the visualized delivery allows for adaptability, accuracy, and on-target coverage, bringing your test item where it needs to be.
Real-time visualization of gene therapy application by MRI-compatible stereotaxic equipment represents the next stage of CNS surgery and therapy. The ClearPoint® System combines specialized MRI-compatible hardware and software to plan trajectories and align and guide the infusion cannula to its target. The cannulas and insertion approach are specifically designed to minimize backflow. Dose volume, infusion rates, and targeting can be optimized throughout this minimally invasive neurosurgery to improve tissue coverage and therapeutic efficacy.
This technology is already in use in the clinical environment providing the translational functionality necessary to bridge preclinical safety pharmacology and toxicology with future patients. The disease indications are countless, but already include brain tumors, epilepsy, Parkinson’s, and other movement disorders. CNS drug discovery is an exciting field, but it is also a challenging one. With recent advances in both CNS targeted drugs and delivery techniques, there is now a huge potential over the next decade for major leaps in CNS disease treatment. Time will tell where the research takes us, but hopefully toward new therapies for difficult to treat and incurable disorders.
An example of a procedure in the left section of the forebrain as follows: targeting of the region of interest (left), gadolinium infusion with cannula trajectory overlaid in three planes (middle), and axial view of targeted gadolinium infusion (right).
The article was written by Jerneja Stare, PhD, Study Director and MRI Targeting Scientist, and Erik Larson, Scientist II and Study Director. Both work at Charles River Laboratories.