March 15, 2010
Research pioneered by FSH Society leads to new discoveries using non-invasive MRI/MRS imaging of FSHD.
“Only fat infiltrated muscles in resting lower leg of FSHD patients show disturbed energy metabolism” is made possible by the FSH Society Grant: Sam E. and Mary F. Roberts Nutrition Research Fellowship Grant FSHS-SMRF-003
A very interesting paper was recently published in the journal “NMR in Biomedicine” titled: “Only fat infiltrated muscles in resting lower leg of FSHD patients show disturbed energy metabolism.” This pioneering research initiated by FSH Society shows that non-invasive imaging such as MRI and MRS can be used to study the progression of FSHD and proposes several new potential non-invasive biomarkers. The research was conducted at the Department of Radiology and the Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. The research team was lead by Hermien Kan and Dr. Arend Heerschap.
This work was initiated and funded by the FSH Society Sam E. and Mary F. Roberts Nutrition Research Fellowship Grant FSHS-SMRF-003. We thank the Sam E. and Mary F. Roberts foundation for making this work possible and for their grants for nutrition related research on FSHD. This pilot work subsequently picked up substantial funding from the Dutch government on FSHD.
In the research study the Dutch researchers have applied for the first time 31P MR spectroscopy to FSHD patients. With 31P MRS one obtains spectra with signals of important phosphorylated compounds such as ATP (key energy donor), phosphocreatine (key energy buffer in muscles) and inorganic phosphate (important in regulations of energy pathways such as of mitochondria). In addition this data provides the pH (acidity) in the muscle cells.
This was also done for the first time in a localized way, i.e. the researchers could measure spectra from several individual muscles separately. The researchers observed the following abnormalities in FSHD muscles (lower leg):
1.) a decrease in the energy buffer PCr, and,
2.) an increase in pH (less acid).
Furthermore, these changes were only observed in muscles that were fat infiltrated
(identified from the MR images) in the FSHD patients, which suggest that in FSHD disease progression is truly muscle specific. Non-fat infiltrated muscles in FSHD also had normal 31P MR spectra.
The 31P MRS observations point to an energy problem in the affected muscles. Similar abnormalities in phosphocreatine and pH have been observed for other muscular dystrophies and thus are not disease specific. In FSHD, the researchers did not find an increase in inorganic phosphate, which is commonly found in other dystrophies. Possibly, this may be considered as more disease specific. It also seems that the abnormalities are related with the severity that the muscles are affected.
Dutch researchers will continue with work to identify these findings better and to investigate what the origin of the abnormalities are, i.e. by light exercise of the
affected muscles. And also to see if treatments, improving muscle performance can be detected early by an effect on MR abnormalities.
All in all a very interesting paper on several new non-invasive biomarkers. This gives us, the FSHD community, credence and specificity when designing clinical trials and show how clinical trials endpoints can be measured and ascertained. It also brings MRI/MRS more into the picture as a tool for such.
See Paper at Wiley InterScience
Only fat infiltrated muscles in resting lower leg of FSHD patients show disturbed energy metabolism.
Kan HE, Klomp DW, Wohlgemuth M, van Loosbroek-Wagemans I, van Engelen BG, Padberg GW, Heerschap A.
Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
NMR Biomed. 2010 Feb 19. [Epub ahead of print]
