The Experts below are selected from a list of 183 Experts worldwide ranked by ideXlab platform
Bouchra Gharib - One of the best experts on this subject based on the ideXlab platform.
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Long-Term Pantethine Treatment Counteracts Pathologic Gene Dysregulation and Decreases Alzheimer’s Disease Pathogenesis in a Transgenic Mouse Model
Neurotherapeutics, 2019Co-Authors: Kevin Baranger, Michel Khrestchatisky, Bouchra Gharib, Max De Reggi, Manuel Gijsel-bonnello, Delphine Stephan, Wassila Carpentier, Santiago Rivera, Philippe BenechAbstract:The low-molecular weight thiol Pantethine, known as a hypolipidemic and hypocholesterolemic agent, is the major precursor of co-enzyme A. We have previously shown that Pantethine treatment reduces amyloid-β (Aβ)-induced IL-1β release and alleviates pathological metabolic changes in primary astrocyte cultures. These properties of Pantethine prompted us to investigate its potential benefits in vivo in the 5XFAD (Tg) mouse model of Alzheimer’s disease (AD).1.5-month-old Tg and wild-type (WT) male mice were submitted to intraperitoneal administration of Pantethine or saline control solution for 5.5 months. The effects of such treatments were investigated by performing behavioral tests and evaluating astrogliosis, microgliosis, Αβ deposition, and whole genome expression arrays, using RNAs extracted from the mice hippocampi. We observed that long-term Pantethine treatment significantly reduced glial reactivity and Αβ deposition, and abrogated behavioral alteration in Tg mice. Moreover, the transcriptomic profiles revealed that after Pantethine treatment, the expression of genes differentially expressed in Tg mice, and in particular those known to be related to AD, were significantly alleviated. Most of the genes overexpressed in Tg compared to WT were involved in inflammation, complement activation, and phagocytosis and were found repressed upon Pantethine treatment. In contrast, Pantethine restored the expression of a significant number of genes involved in the regulation of Αβ processing and synaptic activities, which were downregulated in Tg mice. Altogether, our data support a beneficial role for long-term Pantethine treatment in preserving CNS crucial functions altered by Aβ pathogenesis in Tg mice and highlight the potential efficiency of Pantethine to alleviate AD pathology.
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Long-Term Pantethine Treatment Counteracts Pathologic Gene Dysregulation and Decreases Alzheimer's Disease Pathogenesis in a Transgenic Mouse Model.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2019Co-Authors: Kevin Baranger, Michel Khrestchatisky, Bouchra Gharib, Max De Reggi, Delphine Stephan, Wassila Carpentier, Santiago Rivera, Manuel Van Gijsel-bonnello, Philippe BenechAbstract:The low-molecular weight thiol Pantethine, known as a hypolipidemic and hypocholesterolemic agent, is the major precursor of co-enzyme A. We have previously shown that Pantethine treatment reduces amyloid-β (Aβ)-induced IL-1β release and alleviates pathological metabolic changes in primary astrocyte cultures. These properties of Pantethine prompted us to investigate its potential benefits in vivo in the 5XFAD (Tg) mouse model of Alzheimer’s disease (AD).1.5-month-old Tg and wild-type (WT) male mice were submitted to intraperitoneal administration of Pantethine or saline control solution for 5.5 months. The effects of such treatments were investigated by performing behavioral tests and evaluating astrogliosis, microgliosis, Αβ deposition, and whole genome expression arrays, using RNAs extracted from the mice hippocampi. We observed that long-term Pantethine treatment significantly reduced glial reactivity and Αβ deposition, and abrogated behavioral alteration in Tg mice. Moreover, the transcriptomic profiles revealed that after Pantethine treatment, the expression of genes differentially expressed in Tg mice, and in particular those known to be related to AD, were significantly alleviated. Most of the genes overexpressed in Tg compared to WT were involved in inflammation, complement activation, and phagocytosis and were found repressed upon Pantethine treatment. In contrast, Pantethine restored the expression of a significant number of genes involved in the regulation of Αβ processing and synaptic activities, which were downregulated in Tg mice. Altogether, our data support a beneficial role for long-term Pantethine treatment in preserving CNS crucial functions altered by Aβ pathogenesis in Tg mice and highlight the potential efficiency of Pantethine to alleviate AD pathology.
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Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation
Medical science monitor basic research, 2017Co-Authors: Mhamad Abou-hamdan, Bouchra Gharib, Marc Bajénoff, Valérie Julia, Max De ReggiAbstract:Background: Migration of leukocytes into airways is the hallmark of allergic asthma. The aim of this study was to target the pathological process using Pantethine, a pleiotropic natural compound which has been recently shown to down-regulate chemokine-driven T cell migration.& para;& para;Material/Methods: Mice were sensitized to the Leishmania LACK antigen, then treated or not treated with Pantethine and exposed to LACK or saline aerosol. After sacrifice of the animals, cells in the bronchoalveolar lavage were analyzed and inflammatory parameters were determined to evaluate inflammation seriousness.& para;& para;Results: As compared to untreated animals, Pantethine-treated animals displayed a moderated response to the allergen, as documented by decreased infiltration of inflammatory cells (all types), in addition to reduced levels of lung Th2 cytokines and circulating LACK-specific IgE.& para;& para;Conclusions: These data reveal the potential therapeutic importance of Pantethine to moderate allergic asthma pathology. The compound has been previously shown to exert a broad range of protective activity in animals and in humans, with few or no adverse effects.
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HIF-1α protein levels in Tg and WT astrocytes.
2017Co-Authors: Manuel Van Gijsel-bonnello, Michel Khrestchatisky, Max De Reggi, Kevin Baranger, Santiago Rivera, Philippe Benech, Bouchra GharibAbstract:(A) Western blot analysis of HIF-1α expression in astrocytes treated or not with Pantethine. (B) Densitometric analysis of western blots. Data were normalized to β-actin and are displayed as fold increase relative to untreated WT astrocytes (black diagram). The results represent the mean ± SD from three independent experiments (n = 3 per group) (*, significant difference with the WT control group; #, significant difference with the corresponding group untreated with Pantethine; p
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Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism
Frontiers in oncology, 2016Co-Authors: Marie-france Penet, Bouchra Gharib, Franca Podo, Max De Reggi, Balaji Krishnamachary, Flonne Wildes, Yelena Mironchik, Delia Mezzanzanica, Zaver M. BhujwallaAbstract:Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here we have assessed the effect of Pantethine on tumor growth and metabolism using magnetic resonance imaging (MRI) and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. We therefore used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with Pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were approximately 100 mm3, and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution 1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, Pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of Pantethine and to better understand its mechanism of action.
Toshikazu Kamiya - One of the best experts on this subject based on the ideXlab platform.
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Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation
Vascular health and risk management, 2014Co-Authors: Malkanthi Evans, John A. Rumberger, Joseph J Napolitano, Isao Azumano, Danielle Citrolo, Toshikazu KamiyaAbstract:High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of Pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to Pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16) or placebo. Compared with placebo, the participants on Pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on Pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the Pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that Pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines.
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Pantethine, a derivative of vitamin B5 used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low– to moderate–cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled inv
Nutrition research (New York N.Y.), 2011Co-Authors: John A. Rumberger, Joseph J Napolitano, Isao Azumano, Toshikazu Kamiya, Malkanthi EvansAbstract:Abstract Safety and efficacy of a biologically active derivative of vitamin B 5 (Pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either Pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that Pantethine would lower TC and low-density lipoprotein in low–CVD-risk North American subjects in a similar manner as reported in high–CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, Pantethine demonstrated significant ( P
Max De Reggi - One of the best experts on this subject based on the ideXlab platform.
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Long-Term Pantethine Treatment Counteracts Pathologic Gene Dysregulation and Decreases Alzheimer’s Disease Pathogenesis in a Transgenic Mouse Model
Neurotherapeutics, 2019Co-Authors: Kevin Baranger, Michel Khrestchatisky, Bouchra Gharib, Max De Reggi, Manuel Gijsel-bonnello, Delphine Stephan, Wassila Carpentier, Santiago Rivera, Philippe BenechAbstract:The low-molecular weight thiol Pantethine, known as a hypolipidemic and hypocholesterolemic agent, is the major precursor of co-enzyme A. We have previously shown that Pantethine treatment reduces amyloid-β (Aβ)-induced IL-1β release and alleviates pathological metabolic changes in primary astrocyte cultures. These properties of Pantethine prompted us to investigate its potential benefits in vivo in the 5XFAD (Tg) mouse model of Alzheimer’s disease (AD).1.5-month-old Tg and wild-type (WT) male mice were submitted to intraperitoneal administration of Pantethine or saline control solution for 5.5 months. The effects of such treatments were investigated by performing behavioral tests and evaluating astrogliosis, microgliosis, Αβ deposition, and whole genome expression arrays, using RNAs extracted from the mice hippocampi. We observed that long-term Pantethine treatment significantly reduced glial reactivity and Αβ deposition, and abrogated behavioral alteration in Tg mice. Moreover, the transcriptomic profiles revealed that after Pantethine treatment, the expression of genes differentially expressed in Tg mice, and in particular those known to be related to AD, were significantly alleviated. Most of the genes overexpressed in Tg compared to WT were involved in inflammation, complement activation, and phagocytosis and were found repressed upon Pantethine treatment. In contrast, Pantethine restored the expression of a significant number of genes involved in the regulation of Αβ processing and synaptic activities, which were downregulated in Tg mice. Altogether, our data support a beneficial role for long-term Pantethine treatment in preserving CNS crucial functions altered by Aβ pathogenesis in Tg mice and highlight the potential efficiency of Pantethine to alleviate AD pathology.
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Long-Term Pantethine Treatment Counteracts Pathologic Gene Dysregulation and Decreases Alzheimer's Disease Pathogenesis in a Transgenic Mouse Model.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2019Co-Authors: Kevin Baranger, Michel Khrestchatisky, Bouchra Gharib, Max De Reggi, Delphine Stephan, Wassila Carpentier, Santiago Rivera, Manuel Van Gijsel-bonnello, Philippe BenechAbstract:The low-molecular weight thiol Pantethine, known as a hypolipidemic and hypocholesterolemic agent, is the major precursor of co-enzyme A. We have previously shown that Pantethine treatment reduces amyloid-β (Aβ)-induced IL-1β release and alleviates pathological metabolic changes in primary astrocyte cultures. These properties of Pantethine prompted us to investigate its potential benefits in vivo in the 5XFAD (Tg) mouse model of Alzheimer’s disease (AD).1.5-month-old Tg and wild-type (WT) male mice were submitted to intraperitoneal administration of Pantethine or saline control solution for 5.5 months. The effects of such treatments were investigated by performing behavioral tests and evaluating astrogliosis, microgliosis, Αβ deposition, and whole genome expression arrays, using RNAs extracted from the mice hippocampi. We observed that long-term Pantethine treatment significantly reduced glial reactivity and Αβ deposition, and abrogated behavioral alteration in Tg mice. Moreover, the transcriptomic profiles revealed that after Pantethine treatment, the expression of genes differentially expressed in Tg mice, and in particular those known to be related to AD, were significantly alleviated. Most of the genes overexpressed in Tg compared to WT were involved in inflammation, complement activation, and phagocytosis and were found repressed upon Pantethine treatment. In contrast, Pantethine restored the expression of a significant number of genes involved in the regulation of Αβ processing and synaptic activities, which were downregulated in Tg mice. Altogether, our data support a beneficial role for long-term Pantethine treatment in preserving CNS crucial functions altered by Aβ pathogenesis in Tg mice and highlight the potential efficiency of Pantethine to alleviate AD pathology.
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Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation
Medical science monitor basic research, 2017Co-Authors: Mhamad Abou-hamdan, Bouchra Gharib, Marc Bajénoff, Valérie Julia, Max De ReggiAbstract:Background: Migration of leukocytes into airways is the hallmark of allergic asthma. The aim of this study was to target the pathological process using Pantethine, a pleiotropic natural compound which has been recently shown to down-regulate chemokine-driven T cell migration.& para;& para;Material/Methods: Mice were sensitized to the Leishmania LACK antigen, then treated or not treated with Pantethine and exposed to LACK or saline aerosol. After sacrifice of the animals, cells in the bronchoalveolar lavage were analyzed and inflammatory parameters were determined to evaluate inflammation seriousness.& para;& para;Results: As compared to untreated animals, Pantethine-treated animals displayed a moderated response to the allergen, as documented by decreased infiltration of inflammatory cells (all types), in addition to reduced levels of lung Th2 cytokines and circulating LACK-specific IgE.& para;& para;Conclusions: These data reveal the potential therapeutic importance of Pantethine to moderate allergic asthma pathology. The compound has been previously shown to exert a broad range of protective activity in animals and in humans, with few or no adverse effects.
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HIF-1α protein levels in Tg and WT astrocytes.
2017Co-Authors: Manuel Van Gijsel-bonnello, Michel Khrestchatisky, Max De Reggi, Kevin Baranger, Santiago Rivera, Philippe Benech, Bouchra GharibAbstract:(A) Western blot analysis of HIF-1α expression in astrocytes treated or not with Pantethine. (B) Densitometric analysis of western blots. Data were normalized to β-actin and are displayed as fold increase relative to untreated WT astrocytes (black diagram). The results represent the mean ± SD from three independent experiments (n = 3 per group) (*, significant difference with the WT control group; #, significant difference with the corresponding group untreated with Pantethine; p
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Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism
Frontiers in oncology, 2016Co-Authors: Marie-france Penet, Bouchra Gharib, Franca Podo, Max De Reggi, Balaji Krishnamachary, Flonne Wildes, Yelena Mironchik, Delia Mezzanzanica, Zaver M. BhujwallaAbstract:Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here we have assessed the effect of Pantethine on tumor growth and metabolism using magnetic resonance imaging (MRI) and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. We therefore used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with Pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were approximately 100 mm3, and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution 1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, Pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of Pantethine and to better understand its mechanism of action.
Malkanthi Evans - One of the best experts on this subject based on the ideXlab platform.
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Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation
Vascular health and risk management, 2014Co-Authors: Malkanthi Evans, John A. Rumberger, Joseph J Napolitano, Isao Azumano, Danielle Citrolo, Toshikazu KamiyaAbstract:High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of Pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to Pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16) or placebo. Compared with placebo, the participants on Pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on Pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the Pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that Pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines.
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Pantethine, a derivative of vitamin B5 used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low– to moderate–cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled inv
Nutrition research (New York N.Y.), 2011Co-Authors: John A. Rumberger, Joseph J Napolitano, Isao Azumano, Toshikazu Kamiya, Malkanthi EvansAbstract:Abstract Safety and efficacy of a biologically active derivative of vitamin B 5 (Pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either Pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that Pantethine would lower TC and low-density lipoprotein in low–CVD-risk North American subjects in a similar manner as reported in high–CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, Pantethine demonstrated significant ( P
Jingmin Wang - One of the best experts on this subject based on the ideXlab platform.
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Pilot trial on the efficacy and safety of Pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study.
Orphanet journal of rare diseases, 2020Co-Authors: Xuting Chang, Jie Zhang, Yuwu Jiang, Bufan Yao, Jingmin WangAbstract:Objective This study aimed to explore the efficacy and safety of Pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN). Methods A single-arm, open-label study was conducted. All subjects received Pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson's Disease Rating Scale (UPDRS) I-III and Fahn-Marsden (FM) score from baseline to week 24 after treatment. Results Fifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with Pantethine at 60 mg/kg per day, there was no difference in either UPDRS I-III (t = 0.516, P = 0.614) or FM score (t = 0.353, P = 0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z = 2.614, p = 0.009) and FM scores (Z = 2.643, p = 0.008) were slowed. Four patients (26.7%) were evaluated as "slightly improved" by doctors through blinded video assessment. Patients with lower baseline UPDRS I-III or FM scores were more likely to be improved. The quality of life of family members improved after Pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the quality of life of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study. Conclusions Pantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it may delay the progression of motor dysfunction in our study. Pantethine was well-tolerated at 60 mg/kg per day. Trial registration Clinical trial registration number at www.chictr.org.cn :ChiCTR1900021076, Registered 27 January2019, the first participant was enrolled 30 September 2018, and other 14 participants were enrolled after the trial was registered.
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Pilot trial on the efficacy and safety of Pantethine in children with pantothenate kinase-associated neurodegeneration: A single-arm, open-label study.
2020Co-Authors: Xuting Chang, Jie Zhang, Yuwu Jiang, Bufan Yao, Jingmin WangAbstract:Abstract Objective This study aimed to explore the efficacy and safety of Pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN).Methods A single-arm, open-label study was conducted. All subjects received Pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson’s Disease Rating Scale (UPDRS) I–III and Fahn–Marsden (FM) score from baseline to week 24 after treatment.Results Fifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with Pantethine at 60 mg/kg per day, there was no difference in either UPDRS I–III (t = 0.516, P = 0.614) or FM score (t = 0.353, P = 0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z = 2.614, p = 0.009) and FM scores (Z = 2.643, p = 0.008) were slowed. Four patients (26.7%) were evaluated as “slightly improved” by doctors through blinded video assessment. Patients with lower baseline UPDRS I–III or FM scores were more likely to be improved. The living quality of family members improved after Pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the living quality of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study.Conclusions Pantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it could probably delay the progression of motor dysfunction in our study. 26.7% of patients showed slightly improved. Pantethine was well-tolerated at 60 mg/kg per day.
