Abstract Details

Title Non-Invasive Magnetic Resonance Imaging Monitoring of Glycogen Accumulation in a Mouse Model of Pompe Disease

Topic General Neurology

Presentation(s) P3 - Poster Session 3 (11:45 AM-12:45 PM)

Poster/Presentation
Number 2-009

Objective To evaluate the use of the glycogen nuclear Overhauser effect (glycoNOE) magnetic resonance imaging (MRI) for non-invasive glycogen quantification in Pompe disease (PD).

Background PD is a rare, inherited, metabolic, multisystemic disorder caused by a functional deficiency of the lysosomal enzyme responsible for breaking down glycogen into glucose, acid α-glucosidase (GAA). Glycogen accumulation in tissues, particularly heart, skeletal and smooth muscle, leads to progressive cardiac, motor, and respiratory dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA aims to slow disease progression, and is the only approved treatment modality for PD. Current methods for tracking ERT effects in clearing skeletal muscle glycogen require muscle biopsies. Multiple non-invasive methods have been tested to estimate glycogen levels in vivo, including proton magnetic resonance spectroscopy and ultrasound; however, these methods suffer from low detection sensitivity. Recently, it was demonstrated that glycogen levels can be assessed non-invasively with enhanced sensitivity by utilizing the magnetic coupling between aliphatic protons of glycogen and water protons through the relayed nuclear Overhauser effect.

Design/Methods Previous glycoNOE experiments in a mouse model of glycogen storage disease type III demonstrated the quantification and high-resolution mapping of glycogen levels in these mice. A separate preliminary study tested glycoNOE in human muscles. Here, we evaluate the use of glycoNOE to quantify skeletal muscle glycogen in a mouse model of Pompe disease by testing GAA knockout mice, ERT-treated GAA knockout mice, and wild-type controls, to assess the correlation between biochemical glycogen level and glycoNOE signal.

Results GlycoNOE MRI glycogen quantification could discriminate between controls, GAA knockout and ERT-treated GAA knockout mice.

Conclusions This study shows that glycoNOE imaging can detect the ability of ERT treatment to clear glycogen in different muscle groups in GAA knockout mice and serves as a proof of concept for further research. Supported by Amicus Therapeutics, Inc.

Authors/Disclosures
Qing Zeng, PhD PRESENTER	Dr. Zeng has nothing to disclose.
Derek Timm, PharmD	Dr. Timm has received personal compensation for serving as an employee of Amicus Therapeutics.
Tyler Johnson, PhD	Dr. Johnson has received personal compensation for serving as an employee of Amicus Therapeutics. Dr. Johnson has stock in Amicus Therapeutics.
Nickita Mehta, PhD	Dr. Mehta has received personal compensation for serving as an employee of Amicus Therapeutics. Dr. Mehta has stock in Amicus Therapeutics.
Brian Fox, PhD (Amicus Therapeutics)	Dr. Fox has received personal compensation for serving as an employee of Amicus Therapeutics. Dr. Fox has stock in Amicus Therapeutics.
YUGUO LI, PhD	Dr. LI has nothing to disclose.
Nirbhay Yadav, PhD	Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus therapeutics. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Yadav has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Yadav has received research support from Amicus therapeutics. Dr. Yadav has received intellectual property interests from a discovery or technology relating to health care.

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