2. Academic Validation
  3. Neuroprotective Effect of Mas Activation by BIO101 in Vincristine-Induced Small Fiber Neuropathy

Neuroprotective Effect of Mas Activation by BIO101 in Vincristine-Induced Small Fiber Neuropathy

  • J Peripher Nerv Syst. 2025 Sep;30(3):e70055. doi: 10.1111/jns.70055.
Simon Frachet 1 2,  Aurore Danigo 1 2,  Mathilde Latil 3,  Pierre J Dilda 3,  Flavien Bessaguet 4,  Laurence Richard 2,  Franck Sturtz 1,  Laurent Magy 1 2,  Claire Demiot 1 5
Affiliations

Affiliations

  • 1 NeurIT Neuropathies et Innovations Thérapeutiques UR 20218, Faculties of Medicine and Pharmacy, University of Limoges, Limoges, France.
  • 2 Department of Neurology, Reference Center for Rare Peripheral Neuropathies, University Hospital of Limoges, Limoges, France.
  • 3 Biophytis, Sorbonne Université - BC9, Paris, France.
  • 4 UMR INSERM 1083 CNRS 6015 MITOVASC Laboratory, CarMe Team, University of Angers, Angers, France.
  • 5 Transversal and Territorial Therapeutic Education Unit (UTTEP87), University Hospital of Limoges, Limoges, France.
PMID: 40833359 DOI: 10.1111/jns.70055
Abstract

Background and aims: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect that limits the dosage of many Anticancer therapies, such as vincristine. At present, there are no effective pharmacological treatments to prevent CIPN. The Mas receptor (MasR) is expressed in the peripheral nervous system and plays a role in pain modulation. While the antinociceptive properties of MasR activation in CIPN have been documented, its potential neuroprotective effects have not been explored in the peripheral nervous system. BIO101, a highly purified form of the MasR activator 20-hydroxyecdysone, exhibits a positive safety profile in a Phase 1 study without any serious adverse events.

Methods: This study aimed to investigate the neuroprotective effects of BIO101 in a mouse model of vincristine-induced peripheral neuropathy (VIPN). Swiss mice were treated with daily doses of vincristine. VIPN was evaluated through repeated measurements of tactile sensitivity, quantification of intraepidermal nerve fibers (IENF) and dorsal root ganglion (DRG) neurons, and ultrastructural analysis of the sciatic nerve.

Results: Vincristine led to mechanical allodynia and reduced the density of IENF, DRG neurons, and unmyelinated nerve fibers in the sciatic nerve. Prophylactic administration of BIO101 mitigated vincristine-induced symptoms and nerve damage. The neuroprotective effect of BIO101 was nullified when the MasR antagonist A779 was administered; confirming the involvement of MasR.

Interpretation: Therefore, BIO101 emerges as a safe and promising preventive treatment against vincristine-induced small fiber neuropathy.

Keywords

20‐hydroxyecdysone; chemotherapy‐induced peripheral neuropathy; drug repositioning; neuropathic pain; neuroprotection.

Figures
Products