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A New Animal Model Demonstrates Resistance to the Development of Chemotherapy-induced Peripheral Neuropathy - MRL/MpJ Mice Strain
David Milek
Jonathan Leckenby
University of Rochester
2023-01-23
Presenter: David Milek
Affidavit:
This abstract represents pilot project investigating resistance to chemotherapy-induced peripheral neuropathy development in a new animal model. Project was completed in my Plastic Surgery Research Laboratory by resident David Milek.
Director Name: Jonathan Leckenby - Director of Plastic Surgery Research Laboratory at University of Rochester
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction: Chemotherapy induced peripheral neuropathy (CIPN) is an impactful clinical entity affecting 30-70% of patients undergoing cancer treatment. 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 superior outcomes compared to C57/BL6 in myelination or axon irregularity.
Conclusion: Our preliminary data suggest 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 and may open novel mechanistic opportunities targeting the prevention of CIPN. Future long-term studies are required to determine whether this is long-lasting.
