Novel Metabolic Muscular Biomarkers in Pompe Disease - a Non-invasive Magnetic Resonance Exploratory Pilot Study.

Previous studies have indicated that 13C-MRS in the ultra-high 7T magnetic resonance (MR) field is a potential non-invasive measurement method for assessing changes in muscle glycogen levels in PoD patients. However, in a single study, increases in glycogen intermediates were observed using the even more sensitive 31P-MRS technique in a mouse model of PoD and in glycogen storage disease III in humans. In fact, glycolytic intermediates such as phosphomonoesters (PME), measured by phosphorus-31P-MRS in PoD mouse models, were superior to 13C-MRS in monitoring disease progression and quantifying glycogen, indicating a significant clinical potential of 31P-MRS in humans. It has been shown that 31P-MRS can reliably quantify age- and weight-related differences as well as changes in thyroid function in human muscle metabolism. This study conducted by our institute demonstrates that the technique possesses the necessary sensitivity to measure these subtle muscular metabolic changes. However, there are currently no human 31P-MRS muscle data available for PoD. Therefore, we propose a proof-of-principle study to address this knowledge gap and contribute to establishing a new sensitive muscular biomarker that quantifies the primary disease mechanism, namely glycogen formation, for future longitudinal studies on PoD.


Eligibility Criteria:
Inclusion criteria

Patients with PoD and McArdle disease:

* age between 18-70
* Confirmed diagnosis: enzyme activity and/or genetic testing
* body weight \> 40kg at screening
* 6-minute walking distance \> 75m at screening (only PoD patients)
* Sitting FCV ≥ 30% predicted (only PoD patients)
* "Informed Consent" issued orally and in writing

Healthy volunteers (controls):

• age between 18-70

Exclusion criteria

Patients with PoD and McArdle disease:

* pregnancy (will be assessed prior to MRS measurements using a rapid pregnancy test)
* Involvement of the respiratory musculature
* claustrophobia
* active participation in another clinical trial
* metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation \[heart pacemaker, coronary stents and heart valves (in case these devices are not compatible with a 7T MRI), brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body.

Healthy volunteers (controls):

* any known endocrine, metabolic or neurological disorder
* special diets especially ketogenic or atkins diet
* creatine supplementation
* pregnancy (will be assessed prior to MRS measurements using a rapid pregnancy test)
* claustrophobia
* active participation in another clinical trial
* metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation \[heart pacemaker, coronary stents and heart valves (in case these devices are not compatible with a 7T MRI), brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body.