Similar but not the same: Why are specific muscles less susceptible to damage than others in muscular dystrophies?

Muscular dystrophies (MDs) are characterized by muscle degeneration which
starts in specific muscles and spreads to others as the disease progresses.
Virtually all MDs lack an effective therapy. The order in which muscles
degenerate differs between MDs. The reason for the disease-specific involvement
pattern is unknown and the pathophysiology of the muscle degeneration process
is incompletely understood. Elucidation of this phenomenon could hold the key
for the development of new therapies, by stimulating protective characteristics
in early involved muscles to resemble those in preserved muscles.
We hypothesize that differences in the molecular constitution of muscles
significantly explain differential involvement of skeletal muscles in MDs. This
constitution can be identified using molecular approaches by generating
reference profiles in healthy subjects. Assessment in healthy muscle is
essential as in diseased muscle, tissue changes due to the disease will mask
the constitutive differences between muscles.

1. Compare molecular signatures in six leg muscles using RNA-sequencing;
2. Correlate these signatures to the muscle involvement pattern in three
muscular dystrophies and identify regulators for muscle strength preservation

Proof of concept
Three percutaneous muscle biopsies, two muscles sampled directly from the graft
and one using a incision needed for ACL surgery, all performed during the
surgery procedure and in the surgical area

In this study, biopsies will be taken from six muscles during surgery of the
knee. As the material from two of these muscles, the Gracilis and
Semitendinosus, is directly from the graft they will pose no extra burden. The
other five muscles, the Gastrocnemius Medialis and Lateralis, and Biceps
Femoris Short Head, Vastus Lateralis and Rectus Femoris, are in the direct
vicinity of the operational area. As biopsies will be performed using a
percutaneous biopsy with a minimally invasive biopsy needle, will pose a
minimal extra burden on the participants. A short questionnaire about athletic
activity and the presence of exclusion criteria will be filled out prior to
participation, which will cost extra time for the patients.