Tuesday, 25 October 2022 11:37

ALS disease model demonstrates reduced muscle contractile strength Featured

Using an organ-on-a-chip system, scientists at the startup Hesperos and the University of Central Florida in Orlando have found out, that skeletal muscle plays an important role in ALS disease independent of motor neurons. The finding could make an important contribution to future therapy for ALS and similar diseases.

For their studies, the research team led by Prof. James Hickman first grew motoneurons and muscle cells co-cultured from human induced pluripotent stem cells of healthy volunteers and ALS patients. They used the motor neurons and skeletal muscles in a multifluidic system to investigate the functionality of the so-called neuromuscular connection between these two cell types. The neuromuscular connection between the motoneuron and the skeletal muscle is responsible for the transmission of signals and thus ultimately for movement. In ALS patients, the transmission of signals from the motoneurons to the skeletal muscles is disturbed. This is caused by mutations in up to 50 genes. Until now, there have been different assumptions as to the background of skeletal muscle weakness. For example, it has been assumed that there are pathological motor neurons or that there are malfunctions in the muscle itself.

In their model, the scientists detected evidence of reduced muscle contractility. They were able to measure this by a significantly reduced number and stability of functional neuromuscular connections and by calculating a fatigue index.

Original publication:
Badu-Mensah A, Guo X, Nimbalkar S, Cai Y, Hickman JJ. ALS mutations in both human skeletal muscle and motoneurons differentially affects neuromuscular junction integrity and function. Biomaterials. 2022 Oct;289:121752. doi: 10.1016/j.biomaterials.2022.121752. epub 2022 Aug 19. PMID: 36084484.

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