Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis 
(ALS). Knowledge about the skeletal muscle degeneration/regeneration process and 
the myogenic potential is limited in ALS patients. Therefore, we investigate 
these processes in a time course perspective by analysing skeletal muscle 
biopsies from ALS patients collected before and after a 12-week period of normal 
daily activities and compare these with healthy age-matched control tissue. We 
do this by evaluating mRNA and protein (immunohistochemical) markers of 
regeneration, neurodegeneration, myogenesis, cell cycle regulation, and 
inflammation. Our results show morphological changes indicative of active 
denervation and reinnervation and an increase in small atrophic fibres. We 
demonstrate differences between ALS and controls in pathways controlling 
skeletal muscle homeostasis, cytoskeletal and regenerative markers, 
neurodegenerative factors, myogenic factors, cell cycle determinants, and 
inflammatory markers. Our results on Pax7 and MyoD protein expression suggest 
that proliferation and differentiation of skeletal muscle stem cells are 
affected in ALS patients, and the myogenic processes cannot overcome the 
denervation-induced wasting.