Abstract Details

Title Applicability and Utility of Nerve Conduction Studies in Early Postnatal SMN?7 Mice

Topic Anterior Horn

Presentation(s) P03 - (-)

Poster/Presentation
Number 046

Objective

Background BACKGROUND: Nerve Conduction studies (NCS) provide information about function of the motor unit and have potential as biomarkers for prognostic, predictive, and surrogate marker purposes. NCS are often utilized preclinically in adult mice, but techniques are not established for early postnatal pups. We have modified NCS for use in the SMN?7 mouse-a model of severe spinal muscular atrophy with an average lifespan of <14 days.

Design/Methods DESIGN/METHODS: Studies were performed at postnatal day (PND): 3-5 (n=7), 7 (n=8), and 10-13 (n=15) in SMN?7 (SMN2+/+;Smn?7+/+;mSmn[minus]/[minus]) and control pups (SMN2+/+;Smn?7+/+;mSmn+/[minus]). Mice were anesthetized with isoflurane using a stereotactic rig with nose cone modification for size. CMAP and MUNE are recorded with surface ring electrodes placed over triceps surae using techniques modified for size. Needle electrodes are used for stimulation at the sciatic notch. Supramaximal stimulation is used for CMAP amplitude and submaximal stimulation for incremental MUNE.

Results RESULTS: CMAP amplitudes were reduced in SMN?7 mice but this did not reach statistical significance at early or late time points (Controls: 3.0mV+1.8, 5.7mV+1.8, 8.9mV+3.9 versus SMN?7 1.9mV+1.0, 4.7mV+1.5, and 6.8mV+3.9). MUNE showed significant reduction in estimated motor neurons at PND 10-13 (*p=<0.01) (Controls: 47+26, 81+29, and 190+75 versus SMN?7 45+22, 64+24, and 59*+36).

Conclusions CONCLUSIONS: MUNE reveals similar motor neuron numbers in SMN?7 mice during the early postnatal period and severe motor neuron loss at later time points. Relative preservation of CMAP amplitudes suggest retained potential for axon sprouting and reinnervation in SMN?7 mice. These studies, mirroring those used clinically, are viable tools for motor unit assessment in smaller murine models and will allow translational work to determine the appropriate treatment window and ways to measure treatment response in early phase SMA clinical trials.

Authors/Disclosures
William D. Arnold, MD PRESENTER	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for La Hoffmann Roche. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cadent Therapeutics . Dr. Arnold has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Arnold has received research support from NIH. The institution of Dr. Arnold has received research support from NMD Pharma. The institution of Dr. Arnold has received research support from Gilead Sciences. The institution of Dr. Arnold has received research support from CureSMA. Dr. Arnold has received intellectual property interests from a discovery or technology relating to health care.
	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.
John T. Kissel, MD, FAAN	Dr. Kissel has nothing to disclose.
Arthur H. Burghes, MD (Ohio State University)	No disclosure on file
David Miller	No disclosure on file

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