Muscle regeneration

Muscle regeneration
Muscular dystrophies are characterized by progressive degeneration with regeneration trying to keep up. As there is no cure for muscular dystrophy, it is important to understand the extent of repair in the muscles and if parts of the repair mechanism are affected by the primary disease. In many cases looking regeneration may also offer clues to the extent of the original degeneration. We have studied regeneration in a number of muscular dystrophies and myopathies and found that later stages of regeneration appears to require calpain-3, that up to 40% of muscle fibers can be undergoing active regeneration at any one time and that there likely is a limit to the regenerative mechanism. In order to develop an effective way of activating and boosting the regeneration, we have found in animal models that growth factor activation of muscle stem cells considerably increases muscle mass and that the limiting factor to regeneration in patients with muscular dystrophy likely is myostatin. We are currently utilizing this knowledge in a new enhanced therapy for boosting muscle regeneration.


References

  • Hauerslev S, Vissing J, Krag TO. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model. PLoS One 9(6):e100594 (2014).
  • Krag T, Hauerslev S, Dahlqvist J, Vissing J. Muscle biopsies off-set normal cellular signaling in surrounding musculature. Neuromuscul Disord 2013; 23(12): 981-985.
  • Hauerslev S, Ørngreen MC, Hertz JM, Vissing J, Krag TO. Regeneration and inflammation in skeletal muscle of patients with facioscapulohumeral muscular dystrophy. Acta Neurol Scand 2013; 128(3): 194-201.
  • Krag TO, Hauerslev S, Jeppesen TD, Duno M, Schwartz M, Vissing J. Muscle regeneration in mitochondrial myopathies. Mitochondrion 2013; 13: 63-70.
  • Hauerslev S,Sveen ML,Vissing J, Krag TO. Protein turnover and cellular stress in mildly and severely affected muscles from patients with limb girdle muscular dystrophy type 2I. PLoS One 2013; 8(6): e66929. doi: 10.1371/journal.pone.0066929
  • Anvar SY, Raz Y, Verway N, van der Sluijs B, Venema A, Goeman JJ, Vissing J, van der Maarel SM, ‘t Hoen PA, van Engelen BG, Raz V. A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging. Aging 2013; 5: 412-426.
  • Hauerslev S, Sveen ML, Duno M, Angelini C, Vissing J, Krag TO. Calpain 3 is important for muscle regeneration: Evidence from patients with limb girdle muscular dystrophies. BMC Musculoskelet Disord 2012; 13(1): 43
  • Krag TO, Hauerslev S, Sveen ML, Schwartz M, Vissing J. Level of muscle regeneration in limb-girdle muscular dystrophy type 2I relates to genotype and clinical severity. Skelet Muscle 2011;1:31.