On November 14, 2024, the U.S. Food and Drug Administration (FDA) approved the first gene therapy for aromatic L-amino acid decarboxylase (AADC) deficiency, Kebilidi (generic name: Eladocagene exuparvovec). The product had been marketed as Upstaza™ in Europe, where the European Commission granted approval in November 2022. It is also the first gene therapy the FDA has approved for direct brain injection.
AADC deficiency is a rare and severe genetic disorder affecting neurotransmitter synthesis. Kebilidi uses an adeno-associated virus vector (AAV2) to deliver a functional DDC gene directly to the bilateral striatum. This targeted approach significantly improves patients' motor and cognitive functions. The procedure also depends on knowing where the cannula tip sits during infusion, which is the problem real-time intraoperative MRI (RT-iMRI) navigation addresses.
Core Technology: Features and Advantages of the RT-iMRI System
The Real-time Intraoperative MRI (RT-iMRI) system combines real-time MRI imaging with minimally invasive navigation, and gives brain-targeted therapies a submillimeter working tolerance. Developed by ClearPoint Neuro, the platform pairs high-resolution MRI with dynamic navigation, so a gene vector, drug, or cell suspension can be delivered along a trajectory confirmed against the scan while the infusion runs.
Core Features
1. Real-time Imaging and Navigation
MRI provides real-time 3D visualization of brain structures, offering clinicians and researchers detailed anatomical views. The integrated navigation system updates delivery paths as the procedure proceeds, and guides instruments to the target region.
2. Precision Delivery
Targeting holds to the submillimeter, which matters when the target volume sits beside tissue that has to be preserved. The system also accepts minimally invasive tools such as the SmartFlow Neuro Cannula, which supports delivery efficiency.
3. Dynamic Adjustments and Monitoring
Delivery paths can be adjusted intraoperatively to mitigate anatomical variability or brain tissue shift. Cerebrospinal fluid loss and instrument passage move the target away from the planning scan position, so a fixed coordinate set is not sufficient on its own. MRI imaging monitors the distribution of therapeutic agents, letting the operator confirm that the planned volume has been covered.
Technical Advantages
Precision. The RT-iMRI system achieves micrometer-level accuracy, which matters most in complex brain regions such as the basal ganglia and hippocampus.
Safety. By integrating minimally invasive techniques with real-time imaging, the system minimizes damage to normal brain tissue, reducing complications and recovery times.
Reproducibility. Precise navigation and feedback keep procedures consistent from one subject to the next, which supports reliable data for preclinical research.
Versatility. Beyond gene therapy, RT-iMRI is applicable in neurodegenerative disease research, intracranial cell therapy, and neural circuit modulation.
Prisys Biotech: Pioneering RT-iMRI in NHP Preclinical Research
Prisys Biotech is among the first preclinical CROs in Asia to adopt RT-iMRI technology for nonhuman primate (NHP) studies. By integrating the ClearPoint Brain Navigation System, the Orchestral Head Frame tailored for NHPs, and Convection-Enhanced Delivery (CED) Technology, the company has established a precise platform for intracranial drug and gene delivery. The head frame is what makes the workflow repeatable in animals: a primate skull needs its own fixation geometry, and once registered, planning follows the logic of the clinical procedure.
Platform Advantages
- Precision Localization: RT-iMRI ensures submillimeter accuracy, enabling the delivery of gene vectors, cells, or drugs to target regions through Intracerebral (ICM) Injection, while the trajectory safely crosses the blood-brain barrier.
- Real-time Monitoring: MRI imaging tracks the position of needles or catheters during procedures, reducing tissue damage and improving delivery efficiency.
- Broad Applicability: The platform has been employed in neurodegenerative disease models, hereditary neurological disorder research, and studies exploring intracranial drug distribution and metabolism.
For a sponsor, the practical gain is that delivery becomes a measured variable: catheter placement, infusate spread, and coverage of the target are recorded procedure by procedure. Through its RT-iMRI platform, Prisys Biotech supports preclinical validation of brain-directed therapies and gives research partners imaging and delivery data they can carry into later stages of development.
