Refinement of intrathecal catheter design to enhance neuraxial distribution

• Published in: Journal of neuroscience methods Vol. 402; p. 110006
• Main Authors: Hunt, Matthew A, Hunt, Sara A C, Edinger, Kelly, Steinauer, Joanne, Yaksh, Tony L
• Format: Journal Article
• Language: English
• Published: Netherlands 01.02.2024
• Subjects: Animals; Catheterization - methods; Catheters, Indwelling; Central Nervous System; Humans; Injections, Spinal - methods; Pain; Rats; Intrathecal drug delivery; CNS; Viral vector; Spinal drug delivery; AAV
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2023.110006

Delivery of therapeutics via indwelling intrathecal catheters is highly efficacious for targeting of pain, spasticity, neuraxial cancer and neurodegenerative disorders. However, current catheter designs have some major limitations. Given limited CSF flow, fixed intrathecal volume and the large distance of the rostro-caudal spinal axis, current intrathecal delivery routes fail to achieve adequate drug distribution. Additionally open catheter systems are plagued with cellular ingrowth and debris accumulation if used intermittently. RESULTS/COMPARISON WITH EXISTING METHOD(S): High speed imaging showed micro-valve catheters greatly increase fluid exit velocities compared to typical open-ended catheters, which prevents pooling of injectate proximal to the opening. When implanted intrathecally in rats, small injection volumes (7.5 μL) of dye or AAV9-RFP, resulted in an even rostro-caudal distribution along the spinal axis and robust transfection of neurons from cervical to lumbar dorsal root ganglia. In contrast, such injections with an open-ended catheter resulted in localized distribution and transfection proximal to the delivery site. Our poly micro-valve catheter design resulted in equivalent transfection rates of cervical DRG neurons using 100x lower titer of AAV9-RFP. Unlike open port catheters, no debris accumulation was observed in the lumen of implanted catheters, showing potential for long-term intermittent use. This catheter platform, suitable for small animal models is easily scalable for human use and addresses many of the problems observed with common catheter systems.