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Updated: Nov 30, 2025

Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1
Published on: February 13, 2018
Treatment of Diabetic Neuropathy with A Novel PAR1-Targeting Molecule
Efrat Shavit-Stein1,2, Shany Guly Gofrit2, Alexandra Gayster2
1Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Abstract:
Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1).
Methods:
A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model.
Results:
PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p <0.001), and had hypoalgesia (p <0.05), slow conduction velocity (p <0.0001) and reduced skin innervation (p <0.0001). Treatment with PARIN5 significantly improved rotarod performance (p <0.05), normalized hypoalgesia (p <0.05), attenuated slowing of nerve conduction velocity (p <0.05) and improved skin innervation (p <0.0001).
Conclusion:
PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.
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