Muscular dystrophies are a collection of inherited genetic muscle diseases that are characterized by progressive muscle degeneration and weakness. Skeletal muscle comprises more than 40% of our body weight and is essential for support, physical movement, protection of internal organs, breathing and metabolism. In the Geijsen lab, we study the processes that underlie muscle degeneration and regeneration in the context of degenerating genetic muscle disorders. One of the most prevalent muscle dystrophies is Duchenne muscular dystrophy (DMD). DMD is a devastating muscle wasting disease caused by out-of-frame mutations in the DMD gene. This disease occurs in 1:3,500 male births worldwide. The DMD gene codes for dystrophin, a protein that supports muscle fiber strength, and loss of dystrophin expression causes membrane instability of the muscle fibers. As a result, muscle tissue is lost and patients become wheelchair dependent, lose the ability to use their hands and arms, and ultimately die due to respiratory or cardiac failure in their early to mid-twenties.
Impact
Using genetic muscle disorders as disease model system, we are developing new gene editing technologies with the hope that they can one day contribute to the treatment of DMD and other disorders.
reNEW research
We explore the processes that underlie DMD using murine in vivo models and 3D stem cell-based models of skeletal muscle development. In addition, we’re developing new CRISPR/Cas-based gene editing applications to intervene in the progression of this disorder. We have developed a unique transduction technology (iTOP) for the rapid and highly efficient delivery of recombinant CRISPR/Cas ribonucleoprotein complex (RNP) into skeletal muscles to repair the DMD gene and produce a functional dystrophin protein.
Image description
Murine tibialis anterior muscle. Skeletal muscle fibers (green) are large cylindrical cells formed by the fusion of thousands of nuclei (cyan) during development. These multinucleated cells are surrounded by blood vessels (red) that provide all the nutrients and oxygen necessary for muscle contraction.
Credits
Clara Martinez Mir, PhD student, Geijsen lab, reNEW Leiden.
