Project
Drug-induced muscle function decline
Drugs are prescribed to manage or prevent symptoms and diseases, but may sometimes cause unexpected toxicity to muscles. The symptomatology and clinical manifestations of the myotoxic reaction can very significantly between drugs and between patients on the same drug. This poses a challenge on how to recognise and prevent the occurrence of drug-induced muscle toxicity.
The most prevalent and well-documented drug classes with unintended myotoxicity are the statins, but even today new classes of drugs with unintended myotoxicity are being discovered.
We aim to:
- Improve our understanding how well-known drugs affect muscle functioning and result in muscle symptoms and decreased quality of life.
- Explore which lifestyle measures can be taken to improve muscle function without exacerbating muscle symptoms.
Description
In our research we focus on two main drug categories: statins and tyrosine kinase inhibitors.
By performing detailed human intervention studies in patients on these drugs, we:
- Apply a translational outlook by measuring patients on the whole-body, muscle and cellular level to unravel how muscle functioning is affected by drugs;
- Perform analyses on the tissue/cellular level to better understand the causal mechanism underlying muscle toxicity;
- Relate changes in muscle functioning and molecular targets to changes in muscle symptoms to estimate which processes/ signaling pathways contribute to the muscle symptoms;
- Test various lifestyle approaches to examine whether stimulating muscle functioning can contribute to an improved overall functioning and quality of life without exacerbating muscle symptoms.
All these projects use a combination of techniques such as whole body exercise testing ( muscle dynamometer, cardiopulmonary exercise testing), sampling of body materials (blood and muscle tissue), molecular analyses in blood/ tissue (respiration measurements of isolated muscle fibers, western blotting).
Publications
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Statins affect skeletal muscle performance : Evidence for disturbances in energy metabolism
Journal of Clinical Endocrinology and Metabolism (2017), Volume: 103, Issue: 1 - ISSN 0021-972X - p. 75-84. -
Skeletal muscle toxicity associated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia
Leukemia (2019), Volume: 33 - ISSN 0887-6924 - p. 2116-2120. -
Fatigue in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy : predictors and the relationship with physical activity
Haematologica (2021), Volume: 106, Issue: 7 - ISSN 0390-6078 - p. 1876-1882. -
Muscle Toxicity of Drugs: When Drugs Turn Physiology into Pathophysiology
Physiological reviews (2020), Volume: 100, Issue: 2 - ISSN 0031-9333 - p. 633-672. -
Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users
Journal of the American College of Cardiology (2021), Volume: 78, Issue: 21 - ISSN 0735-1097 - p. 2023-2037. -
Prolonged Moderate-Intensity Exercise Does Not Increase Muscle Injury Markers in Symptomatic or Asymptomatic Statin Users
Journal of the American College of Cardiology (2023), Volume: 81, Issue: 14 - ISSN 0735-1097 - p. 1353-1364. -
The Effect of Exercise Training on Muscle Coenzyme Q10 in Symptomatic and Asymptomatic Statin Users
JACC: Basic to Translational Science (2023), Volume: 8, Issue: 12 - ISSN 2452-302X - p. 1592-1594.