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Senolytic Therapy Improves Chemotherapy-Induced Peripheral Neuropathy

Chemotherapy is well known for causing peripheral neuropathy – a tingling or burning in the hands and feet or perhaps simply numbness in extremities. Now there is evidence that this is caused by Cisplatin and other chemo-drugs inducing a state of senescent-like injury in the dorsal-root ganglia preceding the long nerves to the extremities and that senolytic therapies can mediate recovery of normal sensitivity and function to peripheral nerve systems (at least in mice).

Abstract

“Chemotherapy-induced peripheral neuropathy is among the most common dose-limiting adverse effects of cancer treatment, leading to dose reduction and discontinuation of life-saving chemotherapy and a permanently impaired quality of life for patients. Currently, no effective treatment or prevention is available. Senescence induced during cancer treatment has been shown to promote the adverse effects. Here, we show that cisplatin induces senescent-like neuronal cells in primary culture and in mouse dorsal root ganglia (DRG), as determined by the characteristic senescence markers including senescence-associated beta-galactosidase, accumulation of cytosolic p16INK4A and HMGB1, as well as increased expression of p16Ink4a, p21, and MMP-9. The accumulation of senescent-like neuronal cells in DRG is associated with cisplatin-induced peripheral neuropathy (CIPN) in mice. To determine if depletion of senescent-like neuronal cells may effectively mitigate CIPN, we used a pharmacological ‘senolytic’ agent, ABT263, which inhibits the anti-apoptotic proteins BCL-2 and BCL-xL and selectively kills senescent cells. Our results demonstrated that clearance of DRG senescent neuronal cells reverses CIPN, suggesting that senescent-like neurons play a role in CIPN pathogenesis. This finding was further validated using transgenic p16-3MR mice, which permit ganciclovir (GCV) to selectively kill senescent cells expressing herpes simplex virus 1 thymidine kinase (HSV-TK). We showed that CIPN was alleviated upon GCV administration to p16-3MR mice. Together, the results suggest that clearance of senescent DRG neuronal cells following platinum-based cancer treatment might be an effective therapy for the debilitating side effect of CIPN.”
The full study can be read here: https://rdcu.be/b7ckW

Many of us health nuts are experimenting with available Senolytic compounds. As yet, I have not seen any write-ups on improvement of peripheral neuropathy in self-experimenters with this problem; we should be looking forward to results confirming this in humans.

To your Greater Health and Fitness,

Frank

Frank Wilhelmi
Frank Wilhelmi

Frank Wilhelmi – Retired/consultant electronic engineer researches and reports practical strategies for optimizing health and fitness into advanced age. “I have a passion for living life to the fullest, and helping others to do the same.” A rapidly growing body of knowledge now enables us to extend our health and fitness decades beyond popular expectations.

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