Curcumin was shown to exert beneficial effects on nerve function in peripheral neuropathies. Despite its prominent biological activities, curcumin presents with unfavorable pharmacokinetics. For this purpose, we have developed curcumin-loaded cyclodextrin/cellulose nanocrystals (NanoCur) to bypass this limitation. The current study aims to assess the potency of NanoCur in Charcot-Marie-Tooth disease type 1A (CMT1A) rodent models and compare its efficacy to Theracurmin® (Thera), a commercially available curcumin formulation, while elaborating on its mechanism of action. For that, a low dose of NanoCur was chronically administered for rodents and CMT1A neuropathology was assessed through a battery of functional, histological and biochemical tests. Toxicity and mechanism of action of NanoCur were evaluated both in-vivo & in-vitro. The overall study supports an improved motor function, associated with an amelioration in peripheral myelination in the NanoCur, but not Thera-treated CMT1A animals, combined to a high margin of safety. Furthermore, NanoCur appears to perform its effect through an alleviation of inflammatory pathways, involving macrophage recruitment to the diseased nerve. This study shows that NanoCur associates with therapeutic benefits at the cellular and functional levels in CMT1A with minimal systemic toxicity, promoting it as a potential therapeutic candidate for CMT1A disease and, possibly, other forms of neuropathy.
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