May 11, 2020
Recent publication in ALTEX demonstrates prediction of clinical peripheral neuropathy by chemotherapeutic drugs using NerveSim™ powered by Nerve-on-a-Chip®
Using AxoSim’s NerveSim™ Peripheral Neuropathy Assay, AxoSim scientists showed distinct, mechanistic readouts of four common chemotherapeutics’ neurological effects. As the first 3D in vitro model to collect electrophysiological and histomorphic metrics that are used clinically to assess nerve pathology, NerveSim™ is a biomimetic system that mimics axon growth.
For this study, embryonic rat dorsal root ganglia were used in a 3D NerveSim™ construct. NerveSim™ constructs were then used to test the peripheral neuropathy effects of bortezomib, oxaliplatin, paclitaxel, and vincristine. After 7 days of treatment, axons were electrically stimulated to collect nerve conduction velocity (NCV) and the peak amplitude (AMP), which are two clinical electrophysiological metrics indicative of healthy or diseased populations. Across all four chemotherapeutic drugs, decreased NCV and AMP were observed, even with little or no change in cell viability. At high drug concentrations, NCV and AMP were lower than control values by 10-60%. Histopathological analysis revealed that NerveSim™ exhibits hallmarks of peripheral neuropathy. Acetaminophen and Amoxicillin were used as negative controls and showed minor effects on NCV and AMP. This study demonstrated that AxoSim’s NerveSim PN Assay recapitulates in vivo effects of peripheral neuropathy in an in vitro capacity. As bortezomib, oxaliplatin, paciltaxel, and vincristine all present different toxic signatures, it is particularly noteworthy that the NerveSim™ was able to show clinically relevant presentations of neuropathy in all four compounds. Further studies will probe in greater detail the specific mechanisms by which each drug causes peripheral neuropathy in the NerveSim™.
“This study shows that our NerveSim™ platform has the ability to simulate different presentations of peripheral neuropathy across common chemotherapeutic drugs. We are excited to explore the neurological side effects of more drug categories.”- Dr. Michael J. Moore, AxoSim Co-Founder and Professor of Biomedical Engineering at Tulane University
A study previously confirmed AxoSim’s NerveSim™ powered by Nerve-on-a-Chip® Platform as the first all-human in vitro model with the demonstrated capability to measure critical factors that were formerly only available using live in vivo models. Funded by a Phase 2 NIH NCATS Small Business Technology Transfer Research Grant, this study further shows NerveSim™’s ability to recapitulate specific neurological side effects of chemotherapeutics previously only visible in 2D and in vivo models.
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