Monday, 29 November 2021 10:53

Rare diseases: Myasthenia gravis studied using Organ-on-a-chip Technology Featured

Researchers at the University of Central Florida and at Hesperos, a company based in Orlando, have developed an organ-on-a-chip model to study the mechanisms of the rare autoimmune disease myasthenia gravis.

Myasthenia gravis is a load-dependent muscle weakness that is caused by an impaired transmission from the nerve to the muscle. As a result, muscle tension is disturbed after a nerve stimulus. This is due to the formation of endogenous antibodies that attack receptors on the muscle surface. The disease can manifest in visual disturbances, but can also affect other muscle groups up to the respiratory muscles. The disease is not curable1. However, affected individuals must take immunosuppressive drugs2 and live with limitations, thus improved therapies are needed.

Basic principles, but also possible therapies of this rare disease are mostly investigated with mice so far. Here, for example, injections of the muscle receptor into the animals are used to evoke the very stressful autoimmune reaction in order to treat appearing symptoms.

However, there would be a significant lack of predictive in vivo models that can accurately simulate the disease pathology. This is due to differences between the immune systems of humans and laboratory animals, and because of the high mortality rate of animals due to the severity of the disease, which biases statistical analysis, according to the authors of the current study. Also, individual differences among patients often make personalized medicine necessary.

The researchers developed a coculture model of primary human skeletal muscle and induced pluripotent stem cell (iPSC)-derived motor neurons in a serum-free medium that together mimics a functional neuromuscular junction. The cells were brought together with an antibody against the acetylcholine receptor to induce the disease. The researchers observed that the antibody reduced the stability of the neuromuscular junction. A special role is played by the complement system, which has a complementary function in the antibody response3.

The scientists published their study in the journal Frontiers in Cell and Developmental Biology:
Smith, V.M., Nguyen, H., Rumsey, J.W., Long, C.J., Shuler, M.L. & Hickman, J.J. (2021). A Functional Human-on-a-Chip Autoimmune Disease Model of Myasthenia Gravis for Development of Therapeutics. Front. Cell Dev. Biol. 9:745897. doi:10.3389/fcell.2021.745897


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