Abstract Details

Title Electrical Impedance Myography for High Throughput Drug Screening in ALS Mouse Models

Topic Anterior Horn

Presentation(s) P02 - (-)

Poster/Presentation
Number 169

Objective

Background BACKGROUND: Currently, the evaluation of drug efficacy in ALS mice relies upon demonstrating prolonged survival. However, this approach is inefficient and costly. A tool to rapidly screen drugs early in the disease course could help speed the identification of efficacious therapies. Here we evaluate EIM for this purpose.

Design/Methods DESIGN/METHODS: Forty-seven ALS SOD1 G93A mice were divided into 2 groups: one receiving riluzole 0.2 mg/kg/day and one not. Animals were assessed weekly with EIM, compound motor action potential (CMAP) amplitude, motor unit number estimation (MUNE), and paw grip endurance testing (PGET). Animals were followed until they were too weak to feed at which point they were sacrificed.

Results RESULTS: Two animals died early from non-ALS related causes and were excluded from the analysis. No significant differences between the remaining 23 treated and 22 untreated animals were identified in any of the parameters measured including survival to suggest a riluzole treatment effect; thus, the data from all mice were combined for subsequent analysis. EIM phase showed consistent reductions early in the disease course, but CMAP, MUNE, and PGET did not. As a consequence, by 8 weeks of age, EIM would have an 80% potential power to detect a 30% slowing of disease progression with just 35 animals per group whereas other approaches would require hundreds of animals. Only by about 16-18 weeks of age did a clear downward trend emerge for MUNE, CMAP, and PGET and the sample size estimates begin to approach those of EIM.

Conclusions CONCLUSIONS: Since EIM can consistently detect ALS progression in young mice, it has the potential of serving as a powerful biomarker for assessing therapy efficacy and accelerating the evaluation of promising drugs.

Authors/Disclosures
Seward B. Rutkove, MD, FAAN PRESENTER	Dr. Rutkove has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Myolex, Inc. Dr. Rutkove has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neuorlogy . The institution of Dr. Rutkove has received research support from NIH. The institution of Dr. Rutkove has received research support from NASA. The institution of Dr. Rutkove has received research support from Blavatnik Family Foundation. Dr. Rutkove has received intellectual property interests from a discovery or technology relating to health care. Dr. Rutkove has received intellectual property interests from a discovery or technology relating to health care. Dr. Rutkove has received publishing royalties from a publication relating to health care. Dr. Rutkove has received publishing royalties from a publication relating to health care. Dr. Rutkove has received personal compensation in the range of $500-$4,999 for serving as a Grant Reviewer with NIH.
	No disclosure on file
	No disclosure on file
Paul W. O'Connor, MD	No disclosure on file

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