Researchers at the University of Basel have designed two proteins that can reverse congenital muscular dystrophy and increase the lifespan of mice.
Congenital muscular dystrophy (CMD) englobes several genetic diseases that cause muscle weakness from birth. As patients age, the disease becomes more severe and affects breathing, often leading to death before adulthood. Unfortunately, there are no effective treatments for CMD.
The research group of Prof. Markus Rüegg, at the University of Basel, has a long track of studying CMD and testing new approaches to treating it. Results from its latest study, published today in Science Translational Medicine, reveal that two proteins designed by the scientists can compensate for the genetic defect in mice, recovering muscle force and restoring a normal lifespan.
The study focused on mutations in laminin α2, which are responsible for 30% of CMD cases. This protein is part of the extracellular matrix of muscle fibers, and responsible for anchoring muscle cells to the extracellular matrix that surrounds them. Rüegg and his group had noticed before that when laminin α2 is absent, another protein, laminin α4, can naturally take over and partly replace its function, though it is not sufficient to restore a healthy phenotype.
Muscle biopsy where blood vessels are stained in red and laminin α2 in green, surrounding each muscle fiber
The researchers decided to design two new proteins that can help anchor laminin α4 to the muscle cell and replace laminin α2. The results revealed that mice genetically modified to express these two linkers regained healthy muscle structure and force, and that both their body weight and lifespan increased. “Some of them even survived their healthy siblings,” says Rüegg.
“Both of the designed linker proteins may possibly be used in the future as a gene therapy treatment for congenital muscular dystrophy,” explains Rüegg. “Our study is a nice example of how the understanding of a disease on the molecular and cellular level results in new therapeutic options. We are now interested in whether these linker proteins also improve muscle function as well as affect survival in advanced stages of congenital muscular dystrophy.”