MRI-Guided CNS Delivery in NHP Models | Translational IMRI & CED Platform

Delivering therapeutics to the central nervous system (CNS) remains a central challenge in biopharmaceutical research and development. The blood–brain barrier (BBB) significantly limits the effectiveness of systemic administration, while conventional stereotactic intracranial injections may result in variable distribution, catheter misplacement due to intraoperative brain shift, and limited translational predictability.

To reduce technical risk in CNS programs and support clinical translation, Prisys Biotechnologies has established Asia's first industrial-scale MRI-guided precision CNS delivery platform in Non-Human Primate (NHP) models. By integrating clinical-grade intraprocedural MRI (iMRI) with advanced intracerebral delivery technologies, we provide a translationally aligned framework for evaluating gene therapies (including AAV vectors), cell therapies, nucleic acid therapeutics, and targeted small molecules.

Accurate targeting of deep brain structures is essential for therapeutic efficacy and safety. Traditional frame-based or pre-registered stereotactic approaches rely on preoperative imaging and may be affected by intraoperative brain shift, which can alter catheter trajectory and reduce targeting precision. Prisys addresses this limitation through real-time intraprocedural MRI (iMRI) guidance using the clinically established ClearPoint Neuro navigation platform.

• High Targeting Precision: Real-time trajectory planning and intraoperative adjustment enable precise catheter placement in anatomically complex regions such as the putamen, caudate nucleus, and substantia nigra.
• Intraoperative Visualization: Continuous MRI feedback allows verification of catheter positioning and adjustment in response to anatomical changes during the procedure.

This approach enhances reproducibility and improves the anatomical accuracy of CNS delivery in translational NHP studies.

Direct bolus injection into brain parenchyma primarily depends on passive diffusion, which can lead to limited tissue penetration, heterogeneous distribution, and potential reflux along the catheter tract. Prisys implements Convection-Enhanced Delivery (CED), an approach that uses controlled positive pressure gradients to distribute therapeutics more uniformly within target structures.

• Improved Volume of Distribution: CED enables broader and more homogeneous coverage within defined anatomical regions compared to diffusion-based injection.
• Reduced Reflux Risk: Step-design microcannulas (such as the SmartFlow Cannula) and optimized infusion parameters are employed to minimize backflow and tissue disruption.
• Real-Time Distribution Monitoring: Co-infusion of MRI-visible tracers allows visualization of infusate distribution during and after administration, enabling quantitative coverage assessment.

The objective of preclinical CNS research is to generate data that meaningfully informs clinical trial design. Prisys' CNS delivery platform is structured around translational alignment, utilizing clinically relevant neurosurgical workflows and MRI-compatible hardware consistent with those used in human trials.

Key Translational Advantages:

• Feasibility validation of delivery strategies prior to First-in-Human (FIH) studies.
• Optimization of infusion parameters including rate, volume, and target selection.
• Assessment of safety, distribution, and procedural reproducibility in a large-animal model.

Our CNS programs integrate longitudinal MRI follow-up, CSF sampling, PK/PD assessment, and neurobehavioral evaluation to support robust IND-enabling packages. Applications include bilateral striatal delivery for Huntington's disease and multi-target strategies for neurodegenerative disease programs.

Bridging a promising CNS candidate to clinical evaluation requires a delivery strategy that mirrors clinical practice. By combining large-animal neurosurgical expertise, MRI-guided precision targeting, and controlled CED, Prisys Biotechnologies provides a translationally grounded platform for CNS drug development.

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