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Murphy Roths Large Mice Demonstrate Resistance To The Development Of Paclitaxel-induced Peripheral Neuropathy
David Milek, MD, Angel'Niqua Dixon, BS, Michael Catanzaro, MD, Jonathan Leckenby, MD, PhD.
University of Rochester, Rochester, NY, USA.

PURPOSE:
Chemotherapy induced peripheral neuropathy (CIPN) is an impactful clinical entity affecting 30-70% of patients that often determines the length and dosage of cancer treatment. While an effective treatment against cancer cells, it also has an affinity for peripheral nerve fibers leading to dysfunction or degeneration in 50-70% of patients acutely and 30% of patients chronically. The Murphy Roths Large (MRL/MpJ) strain of mice have demonstrated superior wound healing and peripheral nerve regeneration through resisting the degradation of myelin. This study aims to examine whether the same principles can prevent the development CIPN.
METHODS:
A validated model of CIPN was used to compare, MRL/MpJ (experimental) and C57/BL6 (control) mice. Animals received paclitaxel (PTX) at a total dose of 8mg/kg administered at 2mg/kg for four doses on alternate days (low-dose) or a single 35mg/kg dose (high-dose). Evaluation of allodynia, thermal sensitivity, gait analysis, and electrophysiology was completed. At the 4-week end point sciatic nerves were harvested from both groups for analysis.
RESULTS:
Low-dose animals failed to develop clinical signs of CIPN. In the high dose experiments, C57/BL6 developed significant gait disturbances and thermal sensitivity compared to the MRL/MpJ strain. In both high- and low-doses, the MRL/MpJ demonstrated no significant change in nerve conduction analysis whereas the C57/BL6 had a significantly decreased velocity and increased latency. Histologically, the MRL/MpJ strain demonstrated no significant change in myelination or axon irregularity whereas the C57/BL6 demonstrated significantly decreased myelination and increased irregularity.
CONCLUSION:
This study suggests that future animal models for CIPN should focus in clinically translatable doses. The MRL/MpJ strain has demonstrated a resistance to developing CIPN that is likely due to the prevention of axonal demyelination. Future long-term studies are required to determine whether this is long-lasting. Encouragingly, this strain may open novel mechanistic opportunities that target the prevention of CIPN.


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