The Experts below are selected from a list of 160713 Experts worldwide ranked by ideXlab platform
James J Chen - One of the best experts on this subject based on the ideXlab platform.
-
the liver toxicity Biomarker Study phase i markers for the effects of tolcapone or entacapone
Toxicologic Pathology, 2012Co-Authors: Robert N Mcburney, Carrie L Moland, Ching-wei Chang, Laura K. Schnackenberg, Richard D. Beger, Wade M Hines, James C Fuscoe, Linda S Vontungeln, Tao Han, James J ChenAbstract:The Liver Toxicity Biomarker Study is a systems toxicology approach to discover Biomarkers that are indicative of a drug’s potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a “toxic” drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a “clean” drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed. Comprehensive molecular analysis of rat liver and plasma samples yielded marker analytes for various drug–vehicle or drug–drug comparisons. An important finding was that the marker analytes associated with tolcapone only partially overlapped with marker analytes associated with entacapone, despite the fact that both drugs have similar chemical structures and the same primary pharmacological mechanism of action. This result indicates that the molecular analyses employed in the...
-
the liver toxicity Biomarker Study phase i design and preliminary results
Toxicologic Pathology, 2009Co-Authors: Robert N Mcburney, Carrie L Moland, Ching-wei Chang, Laura K. Schnackenberg, Richard D. Beger, Wade M Hines, Linda S Von Tungeln, James C Fuscoe, James J Chen, Zhenqiang SuAbstract:Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to Studying pharmacological or toxicological effects.
Robert N Mcburney - One of the best experts on this subject based on the ideXlab platform.
-
the liver toxicity Biomarker Study phase i markers for the effects of tolcapone or entacapone
Toxicologic Pathology, 2012Co-Authors: Robert N Mcburney, Carrie L Moland, Ching-wei Chang, Laura K. Schnackenberg, Richard D. Beger, Wade M Hines, James C Fuscoe, Linda S Vontungeln, Tao Han, James J ChenAbstract:The Liver Toxicity Biomarker Study is a systems toxicology approach to discover Biomarkers that are indicative of a drug’s potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a “toxic” drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a “clean” drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed. Comprehensive molecular analysis of rat liver and plasma samples yielded marker analytes for various drug–vehicle or drug–drug comparisons. An important finding was that the marker analytes associated with tolcapone only partially overlapped with marker analytes associated with entacapone, despite the fact that both drugs have similar chemical structures and the same primary pharmacological mechanism of action. This result indicates that the molecular analyses employed in the...
-
the liver toxicity Biomarker Study phase i design and preliminary results
Toxicologic Pathology, 2009Co-Authors: Robert N Mcburney, Carrie L Moland, Ching-wei Chang, Laura K. Schnackenberg, Richard D. Beger, Wade M Hines, Linda S Von Tungeln, James C Fuscoe, James J Chen, Zhenqiang SuAbstract:Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to Studying pharmacological or toxicological effects.
Basil T. Darras - One of the best experts on this subject based on the ideXlab platform.
-
recruitment retention program for the neuronext sma Biomarker Study super babies for sma
Contemporary clinical trials communications, 2018Co-Authors: Amy Bartlett, Sandra P Reyna, Ai Sakonju, Stephen J. Kolb, Kathryn J Swoboda, Allison Kingsley, Basil T. DarrasAbstract:Abstract Background/Aims Recruitment and retention of research participants are challenging and critical components of successful clinical trials and natural history studies. Infants with spinal muscular atrophy (SMA) have been a particularly challenging population to Study due to their fragile and complex medical issues, poor prognosis and, until 2016, a lack of effective therapies. Recruitment of healthy infants into clinical trials and natural history studies is also challenging and sometimes assumed to not be feasible. Methods In 2011, our group initiated a two-year, longitudinal natural history Study of infants with SMA and healthy infant controls to provide data to assist in the analysis and interpretation of planned clinical trials in infants with SMA. The recruitment goal was to enroll 27 infants less than 6 months of age with SMA and 27 age-matched healthy infants within the two-year enrollment period. A detailed recruitment and retention plan was developed for this purpose. In addition, a survey was administered to participant families to understand the determinants of participation in the Study. Results All healthy infants were recruited within the Study's first year and 26 SMA infants were recruited within the two-year recruitment period. Thirty-eight participant families responded to the recruitment determinants survey. Nearly half of respondents (18/38, 48%) reported that they first heard of the Study from their physician or neurologist. The most common reason to decide to enroll their infant (22/38, 58%) and to remain in the Study (28/38, 74%) was their understanding of the importance of the Study. Thematic recruitment tools such as a Study brochure, video on social media, and presentations at advocacy meetings were reported to positively influence the decision to enroll. Conclusions A proactive, thematic and inclusive recruitment and retention plan that effectively communicates the rationale of a clinical Study and partners with patients, advocacy groups and the local communities can effectively recruit participants in vulnerable populations. Recommendations for the proactive integration of recruitment and retention plans into clinical trial protocol development are provided.
-
baseline results of the neuronext spinal muscular atrophy infant Biomarker Study
Annals of clinical and translational neurology, 2016Co-Authors: Stephen J. Kolb, Jon W Yankey, Kristin J Krosschell, Sandra P Reyna, Ai Sakonju, Christopher S Coffey, David W. Arnold, Kathryn J Swoboda, Seward B. Rutkove, Basil T. DarrasAbstract:Objective This Study prospectively assessed putative promising Biomarkers for use in assessing infants with spinal muscular atrophy (SMA). Methods This prospective, multi-center natural history Study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular Biomarkers were assessed at baseline and subsequent visits. Results Enrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 ± 2.2 mV) was significantly reduced compared to controls (5.5 ± 2.0 mV). Electrical impedance myography (EIM) high-frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts. Interpretation By the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit.
Zhenqiang Su - One of the best experts on this subject based on the ideXlab platform.
-
the liver toxicity Biomarker Study phase i design and preliminary results
Toxicologic Pathology, 2009Co-Authors: Robert N Mcburney, Carrie L Moland, Ching-wei Chang, Laura K. Schnackenberg, Richard D. Beger, Wade M Hines, Linda S Von Tungeln, James C Fuscoe, James J Chen, Zhenqiang SuAbstract:Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to Studying pharmacological or toxicological effects.
James C Fuscoe - One of the best experts on this subject based on the ideXlab platform.
-
the liver toxicity Biomarker Study phase i markers for the effects of tolcapone or entacapone
Toxicologic Pathology, 2012Co-Authors: Robert N Mcburney, Carrie L Moland, Ching-wei Chang, Laura K. Schnackenberg, Richard D. Beger, Wade M Hines, James C Fuscoe, Linda S Vontungeln, Tao Han, James J ChenAbstract:The Liver Toxicity Biomarker Study is a systems toxicology approach to discover Biomarkers that are indicative of a drug’s potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a “toxic” drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a “clean” drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed. Comprehensive molecular analysis of rat liver and plasma samples yielded marker analytes for various drug–vehicle or drug–drug comparisons. An important finding was that the marker analytes associated with tolcapone only partially overlapped with marker analytes associated with entacapone, despite the fact that both drugs have similar chemical structures and the same primary pharmacological mechanism of action. This result indicates that the molecular analyses employed in the...
-
the liver toxicity Biomarker Study phase i design and preliminary results
Toxicologic Pathology, 2009Co-Authors: Robert N Mcburney, Carrie L Moland, Ching-wei Chang, Laura K. Schnackenberg, Richard D. Beger, Wade M Hines, Linda S Von Tungeln, James C Fuscoe, James J Chen, Zhenqiang SuAbstract:Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that (a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and (c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to Studying pharmacological or toxicological effects.