Abstract Details

Title Permanent Intrathecal Access in Domestic Piglet for Biomarker and Discovery Studies

Topic General Neurology

Presentation(s) General Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 009

Objective NA

Background The availability of disease modifying therapies for spinal muscular atrophy (SMA) has created an urgent need to identify meaningful biomarkers. Access to cerebrospinal fluid (CSF) for biomarker studies is limited in clinical studies, and large animal models provide opportunities to discover and characterize CSF contents. For longitudinal studies, there is a need for permanent intrathecal access.

Design/Methods

Postnatal day 4 domestic piglets received broad-spectrum antibiotics, steroids, and isoflurane-induced anesthesia prior to surgery. Piglets were placed in prone position over a towel roll with the hips flexed. Following sterile surgical preparation, an incision was made over the lumbosacral area. Soft tissue was dissected and a laminectomy made at the L5 spinal level. The dura was exposed, a micro-incision was made, and CSF egress was visualized. A barium-impregnated, fenestrated catheter was inserted into the thecal sac under direct visualization, then advanced superiorly under fluoroscopic guidance until the tip reached the cisterna magna. Omnipaque dye was injected in the catheter and visualized in the cisterna magna under fluoroscopy. The catheter and access port were flushed with sterile saline and sutured in place subcutaneously. Beginning three days post-surgery, CSF samples were drawn from the port at regular intervals (every 2-4 days) under light anesthesia and analyzed for neurofilament light chain, a biomarker of axonal injury.

Results Catheter patency was maintained, and we collected CSF through the catheters from 7-70 days (study endpoint). Post-mortem dissections confirmed proper catheter placement. Levels of CSF neurofilament light chain at multiple time points will be presented.

Conclusions We have developed a reliable and minimally invasive method for repeated CSF collection in the piglet. Our methodology will enable the study of central and peripheral nervous system conditions where continual access to CSF is desired.

Authors/Disclosures
Megan G. Pino PRESENTER	Ms. Pino has nothing to disclose.
	No disclosure on file
Kelly Rich, MS, CGC	Ms. Rich has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Vibhor Krishna	No disclosure on file
Stephen J. Kolb, MD, PhD (The Ohio State University)	Dr. Kolb has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AveXis. Dr. Kolb has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CureSMA. The institution of Dr. Kolb has received research support from NIH. The institution of Dr. Kolb has received research support from AveXis. The institution of Dr. Kolb has received research support from NIH.

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