Organ-on-a-chip system replicates rare neuromuscular disorders, finds new treatment without animal testing

Good news! This could be a breakthrough for organ on a chip systems to develop new drugs!

"Microphysiological systems, also known as organ-on-a-chip systems, are able to replicate key aspects of the human body and its function. These devices can be used with various living human cells to accelerate drug development, disease modeling, and personalize medicine — and the field is growing fast.
Now, researchers in the United States have used an advanced microphysiological system that mimics the pathology of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy, two very rare but very devastating neuromuscular diseases that cannot be replicated in animal models like rodents or primates. ...
There are over 7,000 rare diseases with no effective treatments, and only about 400 are being actively researched due to a variety of reasons, including the lack of animal models. Moreover, about 9 in 10 drug candidates that show promising results in tests on rodents eventually fail in clinical trials on humans. ..."

From the abstract:

"Chronic autoimmune demyelinating neuropathies are a group of rare neuromuscular disorders with complex, poorly characterized etiology. Here the authors describe a phenotypic, human-on-a-chip (HoaC) electrical conduction model of two rare autoimmune demyelinating neuropathies, chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN), and explore the efficacy of TNT005, a monoclonal antibody inhibitor of the classical complement pathway. Patient sera is shown to contain anti-GM1 IgM and IgG antibodies capable of binding to human primary Schwann cells and induced pluripotent stem cell-derived motoneurons (MNs). Patient autoantibody binding is sufficient to activate the classical complement pathway, resulting in detection of C3b and C5b-9. A HoaC model, using a microelectrode array with directed axonal outgrowth over the electrodes treated with patient sera, exhibits reductions in MN action potential frequency and conduction velocity. TNT005 rescued the serum-induced complement deposition and functional deficits while treatment with an isotype control antibody has no rescue effect. These data indicate that complement activation by CIDP and MMN patient serum is sufficient to mimic neurophysiological features of each disease and that complement inhibition with TNT005 is sufficient to rescue these pathological effects and provide efficacy data included in an investigational new drug application, demonstrating the model's translational potential."

Human-on-a-chip system replicates rare neuromuscular disorders, finds new treatment without animal testing The FDA approved the first clinical trial using efficacy data collected from a microphysiological system. Here's why that's a pretty big deal.

Classical Complement Pathway Inhibition in a “Human-On-A-Chip” Model of Autoimmune Demyelinating Neuropathies (open access)