New therapy option against muscle loss developed
Muscle wasting can sometimes take on life-threatening proportions and so far the treatment options have been very limited. Scientists at the Biozentrum of the University of Basel have now developed two protein building blocks that can be used to treat a special inherited form of muscle weakness. In the animal model, the muscle loss could be successfully stopped with the designed proteins.
"People who suffer from muscle loss often lack essential building blocks in the cell structure," the scientists explain. The cell skeleton, which holds the muscle fibers together and protects them from damage, cannot perform its function, the muscles become weak and increasingly weak. The research team led by Professor Markus Rüegg from the Biozentrum of the University of Basel has now succeeded in stabilizing the cell skeleton with two designed protein building blocks, thus restoring the strength and strength of the muscle tissue. The scientists published their study results in the scientific journal "Science Translational Medicine".
Congenital muscular dystrophy is a severe form of muscle wasting
According to the researchers, the term muscle loss refers to various muscle diseases that are caused by defective genetic makeup. Congenital muscular dystrophy is a rare but very severe form of muscle wasting. The disease occurs immediately after birth or in infancy and those affected are also referred to as "flaccid children" because their muscles have no tension and are weak, explains the first author of the study, Judith Reinhard. The disease worsens with age as the muscles continuously break down. Affected children often never learn to walk independently and the respiratory muscles are also affected, the expert continues.
No medication available for therapy so far
To date, there are no drugs that can stop the progression of congenital muscular dystrophy. The life expectancy is therefore very low and many sufferers die before reaching adulthood, the scientists report. The special form of muscle weakness is based on a genetic defect in the so-called laminin-α2. This central component of the outer cell skeleton connects the latter to the inner part of the muscle fibers and thus ensures the cohesion of the tissue. In the case of gene defects in laminin-α2, the muscles are extremely unstable, according to the scientists, and even normal stress leads to inflammation, damage and, ultimately, the breakdown of the muscle fibers.
Design proteins successfully tested
According to the researchers, people who cannot produce laminin-α2 are replaced by another laminin, which is called laminin-α4. However, this does the job far worse, since it is not very well integrated into the cell skeleton. With the newly developed proteins, however, the scientists in animal models have succeeded in improving the muscle strength and body weight of the diseased animals and significantly extending their lifespan. The two proteins help the laminin-α4 to connect and anchor better with the muscle cell and with each other, the experts explain.
Almost normal life expectancy achieved
"In animals with a laminin α2 defect, muscle tension and strength and body weight improved significantly," reports Professor Rüegg. The connectors were used to stabilize the muscle fibers. “We were particularly pleased to see that the animals treated with the linker proteins have an almost normal life expectancy,” emphasizes the study leader. Some animals were even older than their healthy siblings. "In the future, the two designed linker proteins could possibly be used for gene therapy to treat congenital muscular dystrophy," concludes Prof. Rüegg. (fp)