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Abstract
Discussion Forum (0)
Preclinical Development of a Curcumin-Based Nanoparticle Treatment for Charcot-Marie-Tooth-1A Disease
Poster No: 1187

Presenter: Zeina Msheik
Institution: University of Limoges, EA6309

Introduction: Curcumin has been shown to display antioxidant properties and promyelinating effects in low concentration upon local delivery to the injury site in a sciatic nerve crush rat model. However, given the unfavourable pharmacokinetic of curcumin, we opted for delivering curcumin using a nanoparticle vector. Therefore, curcumin loaded-cyclodextrin (CD)/cellulose (CNC) nanocrystals (Nano-Cur) were synthesized and tested in a rat model of Charcot-Marie-Tooth disease type 1A (CMT1A), the most common hereditary peripheral neuropathy. The first results showed that Nano-Cur was effective in improving sensorimotor symptoms, in increasing myelination and decreasing oxidative stress. Furthermore, Nano-Cur markedly improved curcumin bioavailability, bio-distribution and intracellular delivery.

Methods: In our current study, we aim at investigating the toxicity and confirming the potency of Nano-Cur both in vitro and in preclinical models of the disease.

Results: Preliminary data suggest a low toxicity of both CD and CNC in different cell lines (Schwann cells, fibroblasts, cancer cell line). As a matter of fact, the addition of curcumin into the nanoparticles decreased cellular viability at very high concentrations (30 µM) but not at low concentration (0.15 µM), a concentration that was previously shown to be effective in the enhancement of the disease phenotype in primary CMT1A Schwann cells. In vivo, the potential effects on reversibility of the lesions after a long-term treatment is under investigation in 3-months-old CMT1A rats, and another CMT1A model (i.e. C22 mice) will be used to confirm Nano-Cur efficacy. For this sake, electrophysiological, sensory and motor behavioural measurement are being carried out as well as histopathological examinations in target organs.

Conclusions: Taken together, this project aims at producing Nano-Cur in GLP and later GMP grades, testing its safety, elucidating its mechanisms of action, confirming its efficacy in two CMT1A animal models, while aiming at a translational application for patients with CMT1A and other forms of peripheral neuropathies.

References: Yes
References 1: Caillaud, Martial, et al. 'Curcumin–cyclodextrin/cellulose nanocrystals improve the phenotype of Charcot-Marie-Tooth-1A transgenic rats through the reduction of oxidative stress.' Free Radical Biology and Medicine 161 (2020): 246-262.
References 2:
References 3:
References 4:

Grant Support: AFM-Téléthon

Keywords: Charcot-Marie-Tooth 1A, Peripheral Neuropathies, Nanoparticles Treatment, Curcumin, Pre-clinical studies
Preclinical Development of a Curcumin-Based Nanoparticle Treatment for Charcot-Marie-Tooth-1A Disease
Poster No: 1187

Presenter: Zeina Msheik
Institution: University of Limoges, EA6309

Introduction: Curcumin has been shown to display antioxidant properties and promyelinating effects in low concentration upon local delivery to the injury site in a sciatic nerve crush rat model. However, given the unfavourable pharmacokinetic of curcumin, we opted for delivering curcumin using a nanoparticle vector. Therefore, curcumin loaded-cyclodextrin (CD)/cellulose (CNC) nanocrystals (Nano-Cur) were synthesized and tested in a rat model of Charcot-Marie-Tooth disease type 1A (CMT1A), the most common hereditary peripheral neuropathy. The first results showed that Nano-Cur was effective in improving sensorimotor symptoms, in increasing myelination and decreasing oxidative stress. Furthermore, Nano-Cur markedly improved curcumin bioavailability, bio-distribution and intracellular delivery.

Methods: In our current study, we aim at investigating the toxicity and confirming the potency of Nano-Cur both in vitro and in preclinical models of the disease.

Results: Preliminary data suggest a low toxicity of both CD and CNC in different cell lines (Schwann cells, fibroblasts, cancer cell line). As a matter of fact, the addition of curcumin into the nanoparticles decreased cellular viability at very high concentrations (30 µM) but not at low concentration (0.15 µM), a concentration that was previously shown to be effective in the enhancement of the disease phenotype in primary CMT1A Schwann cells. In vivo, the potential effects on reversibility of the lesions after a long-term treatment is under investigation in 3-months-old CMT1A rats, and another CMT1A model (i.e. C22 mice) will be used to confirm Nano-Cur efficacy. For this sake, electrophysiological, sensory and motor behavioural measurement are being carried out as well as histopathological examinations in target organs.

Conclusions: Taken together, this project aims at producing Nano-Cur in GLP and later GMP grades, testing its safety, elucidating its mechanisms of action, confirming its efficacy in two CMT1A animal models, while aiming at a translational application for patients with CMT1A and other forms of peripheral neuropathies.

References: Yes
References 1: Caillaud, Martial, et al. 'Curcumin–cyclodextrin/cellulose nanocrystals improve the phenotype of Charcot-Marie-Tooth-1A transgenic rats through the reduction of oxidative stress.' Free Radical Biology and Medicine 161 (2020): 246-262.
References 2:
References 3:
References 4:

Grant Support: AFM-Téléthon

Keywords: Charcot-Marie-Tooth 1A, Peripheral Neuropathies, Nanoparticles Treatment, Curcumin, Pre-clinical studies
Preclinical Development of a Curcumin-Based Nanoparticle Treatment for Charcot-Marie-Tooth-1A Disease
Dr. Zeina Msheik
Dr. Zeina Msheik
PNS 2022 Annual Meeting eLibrary. Msheik Z. 04/14/2022; 356040; 1187
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Dr. Zeina Msheik
Abstract
Discussion Forum (0)
Preclinical Development of a Curcumin-Based Nanoparticle Treatment for Charcot-Marie-Tooth-1A Disease
Poster No: 1187

Presenter: Zeina Msheik
Institution: University of Limoges, EA6309

Introduction: Curcumin has been shown to display antioxidant properties and promyelinating effects in low concentration upon local delivery to the injury site in a sciatic nerve crush rat model. However, given the unfavourable pharmacokinetic of curcumin, we opted for delivering curcumin using a nanoparticle vector. Therefore, curcumin loaded-cyclodextrin (CD)/cellulose (CNC) nanocrystals (Nano-Cur) were synthesized and tested in a rat model of Charcot-Marie-Tooth disease type 1A (CMT1A), the most common hereditary peripheral neuropathy. The first results showed that Nano-Cur was effective in improving sensorimotor symptoms, in increasing myelination and decreasing oxidative stress. Furthermore, Nano-Cur markedly improved curcumin bioavailability, bio-distribution and intracellular delivery.

Methods: In our current study, we aim at investigating the toxicity and confirming the potency of Nano-Cur both in vitro and in preclinical models of the disease.

Results: Preliminary data suggest a low toxicity of both CD and CNC in different cell lines (Schwann cells, fibroblasts, cancer cell line). As a matter of fact, the addition of curcumin into the nanoparticles decreased cellular viability at very high concentrations (30 µM) but not at low concentration (0.15 µM), a concentration that was previously shown to be effective in the enhancement of the disease phenotype in primary CMT1A Schwann cells. In vivo, the potential effects on reversibility of the lesions after a long-term treatment is under investigation in 3-months-old CMT1A rats, and another CMT1A model (i.e. C22 mice) will be used to confirm Nano-Cur efficacy. For this sake, electrophysiological, sensory and motor behavioural measurement are being carried out as well as histopathological examinations in target organs.

Conclusions: Taken together, this project aims at producing Nano-Cur in GLP and later GMP grades, testing its safety, elucidating its mechanisms of action, confirming its efficacy in two CMT1A animal models, while aiming at a translational application for patients with CMT1A and other forms of peripheral neuropathies.

References: Yes
References 1: Caillaud, Martial, et al. 'Curcumin–cyclodextrin/cellulose nanocrystals improve the phenotype of Charcot-Marie-Tooth-1A transgenic rats through the reduction of oxidative stress.' Free Radical Biology and Medicine 161 (2020): 246-262.
References 2:
References 3:
References 4:

Grant Support: AFM-Téléthon

Keywords: Charcot-Marie-Tooth 1A, Peripheral Neuropathies, Nanoparticles Treatment, Curcumin, Pre-clinical studies
Preclinical Development of a Curcumin-Based Nanoparticle Treatment for Charcot-Marie-Tooth-1A Disease
Poster No: 1187

Presenter: Zeina Msheik
Institution: University of Limoges, EA6309

Introduction: Curcumin has been shown to display antioxidant properties and promyelinating effects in low concentration upon local delivery to the injury site in a sciatic nerve crush rat model. However, given the unfavourable pharmacokinetic of curcumin, we opted for delivering curcumin using a nanoparticle vector. Therefore, curcumin loaded-cyclodextrin (CD)/cellulose (CNC) nanocrystals (Nano-Cur) were synthesized and tested in a rat model of Charcot-Marie-Tooth disease type 1A (CMT1A), the most common hereditary peripheral neuropathy. The first results showed that Nano-Cur was effective in improving sensorimotor symptoms, in increasing myelination and decreasing oxidative stress. Furthermore, Nano-Cur markedly improved curcumin bioavailability, bio-distribution and intracellular delivery.

Methods: In our current study, we aim at investigating the toxicity and confirming the potency of Nano-Cur both in vitro and in preclinical models of the disease.

Results: Preliminary data suggest a low toxicity of both CD and CNC in different cell lines (Schwann cells, fibroblasts, cancer cell line). As a matter of fact, the addition of curcumin into the nanoparticles decreased cellular viability at very high concentrations (30 µM) but not at low concentration (0.15 µM), a concentration that was previously shown to be effective in the enhancement of the disease phenotype in primary CMT1A Schwann cells. In vivo, the potential effects on reversibility of the lesions after a long-term treatment is under investigation in 3-months-old CMT1A rats, and another CMT1A model (i.e. C22 mice) will be used to confirm Nano-Cur efficacy. For this sake, electrophysiological, sensory and motor behavioural measurement are being carried out as well as histopathological examinations in target organs.

Conclusions: Taken together, this project aims at producing Nano-Cur in GLP and later GMP grades, testing its safety, elucidating its mechanisms of action, confirming its efficacy in two CMT1A animal models, while aiming at a translational application for patients with CMT1A and other forms of peripheral neuropathies.

References: Yes
References 1: Caillaud, Martial, et al. 'Curcumin–cyclodextrin/cellulose nanocrystals improve the phenotype of Charcot-Marie-Tooth-1A transgenic rats through the reduction of oxidative stress.' Free Radical Biology and Medicine 161 (2020): 246-262.
References 2:
References 3:
References 4:

Grant Support: AFM-Téléthon

Keywords: Charcot-Marie-Tooth 1A, Peripheral Neuropathies, Nanoparticles Treatment, Curcumin, Pre-clinical studies

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