In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy, there are malfunctions in the neuromuscular transition from motor neuron to muscle fiber. For a variety of reasons, such as differences in species between humans and animals, a human model is of great importance for the development and selection of effective medications for the treatment of these diseases.

Unlike other tests that investigate neuromuscular function in co-cultures or by biomarker activity and protein analysis, the Hesperos model consists of a functional platform on which human neuronal connections to the skeletal muscle are simulated. The microfluidic device is compartmentalized by a thin silicone membrane with tiny microtunnels forming transitions. Nerve cells (motor neurons) and skeletal muscle cells (myoblasts) grown from human stem cells are placed serum free on the opposite sides of the membrane. Over several days, the muscle cells fuse into muscle fibres (myotubes). The motor neurons send axons (long extensions that conduct electrical impulses away from the nerve cell body) through the microtunnel and form neuromuscular connections with the myotubes. The connections serve as communication channels between the two cell types, similar to the situation in the human body. This way, mini muscles have formed that can be contracted by motor neuron activation or direct electrical stimulation. The model can be used to test pharmaceuticals in single doses or in several doses over a longer period of time to measure how the muscle system reacts.

In a study funded by the National Institutes of Health, dose-response curves were established for three substances (curare toxin, alpha-bungarotoxin and an approved drug, botulinum toxin (BOTOX®)). The results were consistent with available human data and results from clinical studies.

The new technology has been published in the current journal "Biomaterials":

Santhanam, N., Kumanchik, L., Guo, X., Sommerhage, F., Cai, Y., Jackson, M., Martin, C., Saad, G., McAleer, C. W., Wang, Y., Lavado, A., Long, C. J. & Hickman, J. J. (2018). Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics. Biomaterials, accepted manuscript. https://www.ncbi.nlm.nih.gov/pubmed/29547745

Read more here:

http://www.hesperosinc.com/news/2018/4/30/first-functional-stem-cell-derived-neuromuscular-junction-model-licensed