The Experts below are selected from a list of 1425 Experts worldwide ranked by ideXlab platform
Nathalie Guffon - One of the best experts on this subject based on the ideXlab platform.
-
long term follow up on a cohort temporary utilization authorization atu survey of patients treated with pheburane Sodium Phenylbutyrate taste masked granules
Pediatric Drugs, 2016Co-Authors: Yves Kibleur, Nathalie GuffonAbstract:Objectives The aim was to describe the status of patients with urea cycle disorders (UCD) at the latest long-term clinical follow-up of treatment with a new taste-masked formulation of Sodium Phenylbutyrate (NaPB) granules (Pheburane). These patients are a subset of those treated under a cohort temporary utilisation study (ATU) previously reported and now followed for 2 years.
-
results from a nationwide cohort temporary utilization authorization atu survey of patients in france treated with pheburane Sodium Phenylbutyrate taste masked granules
Pediatric Drugs, 2014Co-Authors: Yves Kibleur, Dries Dobbelaere, Magalie Barth, Anais Brassier, Nathalie GuffonAbstract:Objectives The aim of this study was to describe a nationwide system for pre-marketing follow-up (cohort temporary utilization authorization [ATU] protocol; i.e., ‘therapeutic utilization’) of a new taste-masked formulation of Sodium Phenylbutyrate (NaPB) granules (Pheburane®) in France and to analyze safety and efficacy in this treated cohort of patients with urea cycle disease (UCD).
-
developing a new formulation of Sodium Phenylbutyrate
Archives of Disease in Childhood, 2012Co-Authors: Nathalie Guffon, Yves Kibleur, William Copalu, Corinna Tissen, Joerg BreitkreutzAbstract:Background Sodium Phenylbutyrate (NaPB) is used as a treatment for urea cycle disorders (UCD). However, the available, licensed granule form has an extremely bad taste, which can compromise compliance and metabolic control. Objectives A new, taste-masked, coated-granule formulation (Luc 01) under development was characterised for its in vitro taste characteristics, dissolution profiles and bioequivalence compared with the commercial product. Taste, safety and tolerability were also compared in healthy adult volunteers. Results The in vitro taste profile of NaPB indicated a highly salty and bitter tasting molecule, but Luc 01 released NaPB only after a lag time of ∼10 s followed by a slow release over a few minutes. In contrast, the licensed granules released NaPB immediately. The pharmacokinetic study demonstrated the bioequivalence of a single 5 g dose of the two products in 13 healthy adult volunteers. No statistical difference was seen either for maximal plasma concentration (C max ) or for area under the plasma concentration–time curve (AUC). CI for C max and AUC 0–inf of NaPB were included in the bioequivalence range of 0.80–1.25. One withdrawal for vomiting and five reports of loss of taste perception (ageusia) were related to the licensed product. Acceptability, bitterness and saltiness assessed immediately after administration indicated a significant preference for Luc 01 (p Conclusions In vitro dissolution, in vitro and in vivo taste profiles support the view that the newly developed granules can be swallowed before release of the bitter active substance, thus avoiding stimulation of taste receptors. Moreover, Luc 01 was shown to be bioequivalent to the licensed product. The availability of a taste-masked form should improve compliance which is critical to the efficacy of NaPB treatment in patients with UCD.
Yves Kibleur - One of the best experts on this subject based on the ideXlab platform.
-
long term follow up on a cohort temporary utilization authorization atu survey of patients treated with pheburane Sodium Phenylbutyrate taste masked granules
Pediatric Drugs, 2016Co-Authors: Yves Kibleur, Nathalie GuffonAbstract:Objectives The aim was to describe the status of patients with urea cycle disorders (UCD) at the latest long-term clinical follow-up of treatment with a new taste-masked formulation of Sodium Phenylbutyrate (NaPB) granules (Pheburane). These patients are a subset of those treated under a cohort temporary utilisation study (ATU) previously reported and now followed for 2 years.
-
results from a nationwide cohort temporary utilization authorization atu survey of patients in france treated with pheburane Sodium Phenylbutyrate taste masked granules
Pediatric Drugs, 2014Co-Authors: Yves Kibleur, Dries Dobbelaere, Magalie Barth, Anais Brassier, Nathalie GuffonAbstract:Objectives The aim of this study was to describe a nationwide system for pre-marketing follow-up (cohort temporary utilization authorization [ATU] protocol; i.e., ‘therapeutic utilization’) of a new taste-masked formulation of Sodium Phenylbutyrate (NaPB) granules (Pheburane®) in France and to analyze safety and efficacy in this treated cohort of patients with urea cycle disease (UCD).
-
development of a taste masked granule formulation of Sodium Phenylbutyrate adapted for paediatric use
Archives of Disease in Childhood, 2013Co-Authors: N Guffon, Yves Kibleur, William Copalu, Corinna Tissen, Joerg BreitkreutzAbstract:Background Sodium Phenylbutyrate (NaPB), a treatment for urea cycle disorders, has an extremely unpleasant, bitter taste which can compromise compliance and metabolic control, particularly in children. Attempts to mask the taste in food or drinks are unsuccessful and can lead to feeding aversion further complicating management of these serious disorders. Objectives A new, taste-masked, coated-granule formulation (Luc 01) has been developed and the taste characteristics, dissolution and bioequivalence, including taste, safety and tolerability, of this form were compared to the available, licensed granule product. Results The in vitro taste profile of NaPB indicated a highly stimulant molecule. Luc 01 released NaPB only after a lag-time of ∼10 s followed by a very slow release during several minutes compared with complete, immediate release of NaPB from licensed granules. Pharmacokinetic evaluation demonstrated bioequivalence of a 5 g dose of both products in 13 healthy volunteers. No statistical difference was observed for maximal plasma concentration or area under the plasma concentration-time. Luc 01 was significantly more acceptable, less bitter and less salty (p Conclusions In vitro and in vivo taste profiles indicate that Luc 01 can be swallowed before stimulation of taste receptors by NaPB and is bioequivalent to the licensed product. The availability of Luc 01 should improve compliance/efficacy of NaPB treatment and alleviate the burden of administration particularly in children.
-
developing a new formulation of Sodium Phenylbutyrate
Archives of Disease in Childhood, 2012Co-Authors: Nathalie Guffon, Yves Kibleur, William Copalu, Corinna Tissen, Joerg BreitkreutzAbstract:Background Sodium Phenylbutyrate (NaPB) is used as a treatment for urea cycle disorders (UCD). However, the available, licensed granule form has an extremely bad taste, which can compromise compliance and metabolic control. Objectives A new, taste-masked, coated-granule formulation (Luc 01) under development was characterised for its in vitro taste characteristics, dissolution profiles and bioequivalence compared with the commercial product. Taste, safety and tolerability were also compared in healthy adult volunteers. Results The in vitro taste profile of NaPB indicated a highly salty and bitter tasting molecule, but Luc 01 released NaPB only after a lag time of ∼10 s followed by a slow release over a few minutes. In contrast, the licensed granules released NaPB immediately. The pharmacokinetic study demonstrated the bioequivalence of a single 5 g dose of the two products in 13 healthy adult volunteers. No statistical difference was seen either for maximal plasma concentration (C max ) or for area under the plasma concentration–time curve (AUC). CI for C max and AUC 0–inf of NaPB were included in the bioequivalence range of 0.80–1.25. One withdrawal for vomiting and five reports of loss of taste perception (ageusia) were related to the licensed product. Acceptability, bitterness and saltiness assessed immediately after administration indicated a significant preference for Luc 01 (p Conclusions In vitro dissolution, in vitro and in vivo taste profiles support the view that the newly developed granules can be swallowed before release of the bitter active substance, thus avoiding stimulation of taste receptors. Moreover, Luc 01 was shown to be bioequivalent to the licensed product. The availability of a taste-masked form should improve compliance which is critical to the efficacy of NaPB treatment in patients with UCD.
Kalipada Pahan - One of the best experts on this subject based on the ideXlab platform.
-
Sodium Phenylbutyrate enhances astrocytic neurotrophin synthesis via protein kinase c pkc mediated activation of camp response element binding protein creb implications for alzheimer disease therapy
Journal of Biological Chemistry, 2013Co-Authors: Grant T Corbett, Kalipada PahanAbstract:Abstract Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are believed to be genuine molecular mediators of neuronal growth and homeostatic synapse activity. However, levels of these neurotrophic factors decrease in different brain regions of patients with Alzheimer disease (AD). Induction of astrocytic neurotrophin synthesis is a poorly understood phenomenon but represents a plausible therapeutic target because neuronal neurotrophin production is aberrant in AD and other neurodegenerative diseases. Here, we delineate that Sodium Phenylbutyrate (NaPB), a Food and Drug Administration-approved oral medication for hyperammonemia, induces astrocytic BDNF and NT-3 expression via the protein kinase C (PKC)-cAMP-response element-binding protein (CREB) pathway. NaPB treatment increased the direct association between PKC and CREB followed by phosphorylation of CREB (Ser133) and induction of DNA binding and transcriptional activation of CREB. Up-regulation of markers for synaptic function and plasticity in cultured hippocampal neurons by NaPB-treated astroglial supernatants and its abrogation by anti-TrkB blocking antibody suggest that NaPB-induced astroglial neurotrophins are functionally active. Moreover, oral administration of NaPB increased the levels of BDNF and NT-3 in the CNS and improved spatial learning and memory in a mouse model of AD. Our results highlight a novel neurotrophic property of NaPB that may be used to augment neurotrophins in the CNS and improve synaptic function in disease states such as AD.
-
Sodium Phenylbutyrate enhances astrocytic neurotrophin synthesis via protein kinase c pkc mediated activation of camp response element binding protein creb
2013Co-Authors: Grant T Corbett, Kalipada PahanAbstract:Background: Increase in neurotrophic factors in the brain is a possible therapeutic approach for different neurodegenerative disorders. Results: Sodium Phenylbutyrate, an FDA-approved drug for hyperammonemia, increases neurotrophic factors in brain cells via the PKC-CREB pathway. Conclusion: These results delineate a novel neurotrophic property of Sodium Phenylbutyrate. Significance: Sodium Phenylbutyrate may be of therapeutic benefit in neurodegenerative disorders. Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are believed to be genuine molecular mediators of neuronal growth and homeostatic synapse activity. However, levels of these neurotrophic factors decrease in different brain regions of patients with Alzheimer disease (AD). Induction of astrocytic neurotrophin synthesis is a poorly understood phenomenon but represents a plausible therapeutic target because neuronal neurotrophin production is aberrant in AD and other neurodegenerative diseases. Here, we delineate that Sodium Phenylbutyrate (NaPB), a Food and Drug Administration-approved oral medication for hyperammonemia, induces astrocytic BDNF and NT-3 expression via the protein kinase C (PKC)-cAMP-response element-binding protein (CREB) pathway. NaPB treatment increased the direct association between PKC and CREB followed by phosphorylation of CREB (Ser 133 ) and induction of DNA binding and transcriptional activation of CREB. Up-regulation of markers for synaptic function and plasticity in cultured hippocampal neurons by NaPB-treated astroglial supernatants and its abrogation by antiTrkB blocking antibody suggest that NaPB-induced astroglial neurotrophins are functionally active. Moreover, oral administration of NaPB increased the levels of BDNF and NT-3 in the CNS and improved spatial learning and memory in a mouse model of AD. Our results highlight a novel neurotrophic property of NaPB that may be used to augment neurotrophins in the CNS and improve synaptic function in disease states such as AD. Neurotrophins are a class of small, dimeric growth factors essential for the development, maintenance, and function of the
-
Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson’s Disease
PLOS ONE, 2012Co-Authors: Anamitra Ghosh, Arundhati Jana, Saurav Brahmachari, Howard Eliot Gendelman, Kalipada PahanAbstract:Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that Sodium Phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21rac, but not p21ras, attenuated the production of ROS from activated microglia. Inhibition of both p21ras and p21rac activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21ras and p21rac in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Oral administration of NaPB reduced nigral activation of p21ras and p21rac, protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.
-
Sodium Phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of parkinson s disease
PLOS ONE, 2012Co-Authors: Anamitra Ghosh, Kalipada Pahan, Arundhati Jana, Saurav Brahmachari, Howard Eliot GendelmanAbstract:Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that Sodium Phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21rac, but not p21ras, attenuated the production of ROS from activated microglia. Inhibition of both p21ras and p21rac activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21ras and p21rac in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Oral administration of NaPB reduced nigral activation of p21ras and p21rac, protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.
Cheng Yong In - One of the best experts on this subject based on the ideXlab platform.
-
effects of Sodium Phenylbutyrate on differentiation and induction of the p21waf1 cip1 anti oncogene in human liver carcinoma cell lines
Chinese Journal of Digestive Diseases, 2005Co-Authors: Mei Meng, Jun Mei Jiang, Cheng Yong InAbstract:OBJECTIVES: To explore the effects of Sodium Phenylbutyrate on the proliferation, differentiation, cell cycle arrest and induction of the P21WAF1/CIP1 anti-oncogene in human liver carcinoma cell lines Bel-7402 and HepG2. METHODS: Bel-7402 and HepG2 human liver carcinoma cells were treated with Sodium Phenylbutyrate at different concentrations. Light microscopy was used to observe morphological changes in the carcinoma cells. Effects on the cell cycle were detected by using flow cytometry. P21WAF1/CIP1 expression was determined by both reverse transcription–polymerase chain reaction and western blotting. Statistical analysis was performed by using one-way anova and Student's t-test. RESULTS: Sodium Phenylbutyrate treatment caused time- and dose-dependent growth inhibition of Bel-7402 and HepG2 cells. This treatment also caused a decline in the proportion of S-phase cells and an increase in the proportion of G0/G1 cells. Sodium Phenylbutyrate increased the expression of P21WAF1/CIP1. CONCLUSIONS: Sodium Phenylbutyrate inhibits the proliferation of human liver carcinoma cells Bel-7402 and HepG2, induces partial differentiation, and increases the expression of P21WAF1/CIP1.
-
Effects of Sodium Phenylbutyrate on differentiation and induction of the P21WAF1/CIP1 anti-oncogene in human liver carcinoma cell lines.
Chinese Journal of Digestive Diseases, 2005Co-Authors: Mei Meng, Jun Mei Jiang, Cheng Yong InAbstract:OBJECTIVES: To explore the effects of Sodium Phenylbutyrate on the proliferation, differentiation, cell cycle arrest and induction of the P21WAF1/CIP1 anti-oncogene in human liver carcinoma cell lines Bel-7402 and HepG2. METHODS: Bel-7402 and HepG2 human liver carcinoma cells were treated with Sodium Phenylbutyrate at different concentrations. Light microscopy was used to observe morphological changes in the carcinoma cells. Effects on the cell cycle were detected by using flow cytometry. P21WAF1/CIP1 expression was determined by both reverse transcription–polymerase chain reaction and western blotting. Statistical analysis was performed by using one-way anova and Student's t-test. RESULTS: Sodium Phenylbutyrate treatment caused time- and dose-dependent growth inhibition of Bel-7402 and HepG2 cells. This treatment also caused a decline in the proportion of S-phase cells and an increase in the proportion of G0/G1 cells. Sodium Phenylbutyrate increased the expression of P21WAF1/CIP1. CONCLUSIONS: Sodium Phenylbutyrate inhibits the proliferation of human liver carcinoma cells Bel-7402 and HepG2, induces partial differentiation, and increases the expression of P21WAF1/CIP1.
Robert J Ferrante - One of the best experts on this subject based on the ideXlab platform.
-
combined riluzole and Sodium Phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice
Amyotrophic Lateral Sclerosis, 2009Co-Authors: Steven J Del Signore, Merit Cudkowicz, Daniel J Amante, Edward C Stack, Sarah Goodrich, Kerry Cormier, Karen Smith, Robert J FerranteAbstract:Recent evidence suggests that transcriptional dysregulation may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). The histone deacetylase inhibitor, Sodium Phenylbutyrate (NaPB), is neuroprotective and corrects aberrant gene transcription in ALS mice and has recently been shown to be safe and tolerable in ALS patients while improving hypoacetylation. Since many patients are already on riluzole, it is important to ensure that any proposed therapy does not result in negative synergy with riluzole. The combined treatment of riluzole and NaPB significantly extended survival and improved both the clinical and neuropathological phenotypes in G93A transgenic ALS mice beyond either agent alone. Combination therapy increased survival by 21.5%, compared to the separate administration of riluzole (7.5%) and NaPB (12.8%), while improving both body weight loss and grip strength. The data show that the combined treatment was synergistic. In addition, riluzole/NaPB treatment ameliorated gross lumba...
-
Sodium Phenylbutyrate prolongs survival and regulates expression of anti apoptotic genes in transgenic amyotrophic lateral sclerosis mice
Journal of Neurochemistry, 2005Co-Authors: Karen Smith, Merit Cudkowicz, Robert H Brown, Kerry Cormier, Sandra Camelo, Isabel Carreras, Antonio Iglesias, Fernando Dangond, Robert J FerranteAbstract:Multiple molecular defects trigger cell death in amyotrophic lateral sclerosis (ALS). Among these, altered transcriptional activity may perturb many cellular functions, leading to a cascade of secondary pathological effects. We showed that pharmacological treatment, using the histone deacetylase inhibitor Sodium Phenylbutyrate, significantly extended survival and improved both the clinical and neuropathological phenotypes in G93A transgenic ALS mice. Phenylbutyrate administration ameliorated histone hypoacetylation observed in G93A mice and induced expression of nuclear factor-κB (NF-κB) p50, the phosphorylated inhibitory subunit of NF-κB (pIκB) and beta cell lymphoma 2 (bcl-2), but reduced cytochrome c and caspase expression. Curcumin, an NF-κB inhibitor, and mutation of the NF-κB responsive element in the bcl-2 promoter, blocked butyrate-induced bcl-2 promoter activity. We provide evidence that the pharmacological induction of NF-κB-dependent transcription and bcl-2 gene expression is neuroprotective in ALS mice by inhibiting programmed cell death. Phenylbutyrate acts to phosphorylate IκB, translocating NF-κB p50 to the nucleus, or to directly acetylate NF-κB p50. NF-κB p50 transactivates bcl-2 gene expression. Up-regulated bcl-2 blocks cytochrome c release and subsequent caspase activation, slowing motor neuron death. These transcriptional and post-translational pathways ultimately promote motor neuron survival and ameliorate disease progression in ALS mice. Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS.
