Brain, behavior, and immunity
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Brain Behav. Immun. · Mar 2021
Nasal administration of mesenchymal stem cells reverses chemotherapy-induced peripheral neuropathy in mice.
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequently reported adverse effects of cancer treatment. CIPN often persists long after treatment completion and has detrimental effects on patient's quality of life. There are no efficacious FDA-approved drugs for CIPN. ⋯ Moreover, WT MSC do not reverse CIPN in mice lacking IL-10 receptors on peripheral sensory neurons. In conclusion, only two nasal administrations of MSC fully reverse CIPN and the associated mitochondrial abnormalities via an IL-10 dependent pathway. Since MSC are already applied clinically, we propose that nasal MSC treatment could become a powerful treatment for the large group of patients suffering from neurotoxicities of cancer treatment.
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Brain Behav. Immun. · Mar 2021
Targeting Peroxisome Proliferator-Activated Receptor-α (PPAR- α) to reduce paclitaxel-induced peripheral neuropathy.
Paclitaxel, a widely used anti-cancer drug, is frequently associated with prolonged and severe peripheral neuropathies (PIPN), associated with neuroinflammation. Currently, PIPN effective treatments are lacking. Peroxisome Proliferator-Activated Receptor-α (PPAR-⍺) can modulate inflammatory responses. Thus, the use of PPAR-⍺ agonists, such as fibrates (fenofibrate and choline-fenofibrate), currently used in dyslipidemia treatment, could represent an interesting therapeutic approach in PIPN. ⋯ Taken together, our results show for the first time the therapeutic potential (prevention and reversal) of fibrates in PIPN and opens to a potential pharmacological repurposing of these drugs.