Simon Frachet, Aurore Danigo, Mathilde Latil, Pierre J. Dilda, Flavien Bessaguet, Laurence Richard, Franck Sturtz, Laurent Magy, Claire Demiot
{"title":"BIO101激活Mas对长春新碱诱导的小纤维神经病的神经保护作用","authors":"Simon Frachet, Aurore Danigo, Mathilde Latil, Pierre J. Dilda, Flavien Bessaguet, Laurence Richard, Franck Sturtz, Laurent Magy, Claire Demiot","doi":"10.1111/jns.70055","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aims</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>Therefore, BIO101 emerges as a safe and promising preventive treatment against vincristine-induced small fiber neuropathy.</p>\n </section>\n </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 3","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70055","citationCount":"0","resultStr":"{\"title\":\"Neuroprotective Effect of Mas Activation by BIO101 in Vincristine-Induced Small Fiber Neuropathy\",\"authors\":\"Simon Frachet, Aurore Danigo, Mathilde Latil, Pierre J. 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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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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. 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Neuroprotective Effect of Mas Activation by BIO101 in Vincristine-Induced Small Fiber Neuropathy
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.
期刊介绍：
The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders.
The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies.
Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials.
The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
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