Friday, 22 April 2022 12:34

Florida: New neuropathy model on-chip for drug studies of rare diseases Featured

A cell-based neuropathy disease model on-chip developed by Hesperos Inc. in Florida and colleagues is able to successfully recapitulate the neurophysiological features of two rare autoimmune demyelinating neuropathies. Additionally, it has been shown that the model is suitable for assessing the efficacy of new therapeutics.

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are rare, autoimmune neuropathies that manifest in muscle weakness, often associated with walking difficulties and impairment of hand function. The underlying cause is hyperactivity of the immune system due to the production of autoantibodies, resulting in demyelination of the peripheral nerve and a reduction in nerve conduction velocity.

For their model of peripheral motor neuron conduction velocity, the team of researchers from Hesperos Inc., the University of Central Florida, Duke University in Durham, the University of North Carolina, and Sanofi developed motor neurons from induced pluripotent stem cells and used them together with Schwann cells in a microfluidic system. The cells were then supplied with patients' serum suffering from MMN and CIDP, respectively. This resulted in autoantibody binding triggering a complement cascade that measurably impaired neuronal function. Treatment with a specific antibody developed by Sanofi that inhibits the complement pathway led to a normalization of neuronal function. The results support data on an IND (investigational new drug) application for a clinical trial, submitted by Sanofi, which has been accepted by the FDA.

The model is suitable to reduce animal testing since pharmaceutically active substances in a microfluidic disease model can be used to find a therapy for another disease without the need for animal testing. The U.S. Food and Drug Administration (FDA) expressed openness to such an approach.

Original publication:
Rumsey, J.W., Lorance, C., Jackson, M., Sasserath, T., McAleer, C.W., Long, C.J., Goswami, A., Russo, M.A., Raja, S.M., Gable, K.L., Emmett, D., Hobson-Webb, L.D., Chopra, M., Howard, J.F., Jr, Guptill, J.T., Storek, M.J., Alonso-Alonso, M., Atassi, N., Panicker, S., Parry, G., Hammond, T. &. Hickman, J.J. (2022), Classical complement pathway inhibition in a "human-on-a-chip" model of autoimmune demyelinating neuropathies. Adv. Therap. 2200030.

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