Tarenflurbil

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Michelle M. Nicolle - One of the best experts on this subject based on the ideXlab platform.

  • Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice.
    BMC Neuroscience, 2007
    Co-Authors: Thomas Kukar, Sonya Prescott, Jason L. Eriksen, Vallie M. Holloway, M. Paul Murphy, Todd E. Golde, Michelle M. Nicolle
    Abstract:

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (Tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice.

  • Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice
    BMC Neuroscience, 2007
    Co-Authors: Thomas Kukar, Sonya Prescott, Jason L. Eriksen, M. Paul Murphy, Todd E. Golde, Vallie Holloway, Michelle M. Nicolle
    Abstract:

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R -flurbiprofen (Tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R -flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R -flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R -flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R -flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its ability to selectively target Aβ42 production and improve cognitive impairments in transgenic APP mice, as well as promising data from a phase 2 human clinical trial, future studies are needed to investigate the utility of R -flurbiprofen as an AD therapeutic and its possible mechanisms of action.

Thomas Kukar - One of the best experts on this subject based on the ideXlab platform.

  • Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice.
    BMC Neuroscience, 2007
    Co-Authors: Thomas Kukar, Sonya Prescott, Jason L. Eriksen, Vallie M. Holloway, M. Paul Murphy, Todd E. Golde, Michelle M. Nicolle
    Abstract:

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (Tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice.

  • Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice
    BMC Neuroscience, 2007
    Co-Authors: Thomas Kukar, Sonya Prescott, Jason L. Eriksen, M. Paul Murphy, Todd E. Golde, Vallie Holloway, Michelle M. Nicolle
    Abstract:

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R -flurbiprofen (Tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R -flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R -flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R -flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R -flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its ability to selectively target Aβ42 production and improve cognitive impairments in transgenic APP mice, as well as promising data from a phase 2 human clinical trial, future studies are needed to investigate the utility of R -flurbiprofen as an AD therapeutic and its possible mechanisms of action.

Kenton H Zavitz - One of the best experts on this subject based on the ideXlab platform.

  • Effect of Tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial.
    JAMA, 2009
    Co-Authors: Robert C Green, Andrew P Beelen, Gordon Wilcock, Edward A Swabb, David A. Amato, Lon S Schneider, Kenton H Zavitz
    Abstract:

    CONTEXT Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial. OBJECTIVE To determine the efficacy, safety, and tolerability of Tarenflurbil. DESIGN, SETTING, AND PATIENTS A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted. INTERVENTION Tarenflurbil, 800 mg, or placebo, administered twice a day. MAIN OUTCOME MEASURES Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies-activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification. RESULTS Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, -0.9 to 1.1; P = .86 and -0.5 for ADCS-ADL; 95% CI, -1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The Tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections. CONCLUSION Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00105547.

Robert C Green - One of the best experts on this subject based on the ideXlab platform.

  • effect of Tarenflurbil on cognitive decline and activities of daily living in patients with mild alzheimer disease a randomized controlled trial
    JAMA, 2009
    Co-Authors: Robert C Green, Andrew P Beelen, David A. Amato, Lon S Schneider, Gordon K Wilcock, Edward Swabb, Kenton Zavitz
    Abstract:

    Context Amyloid-β peptide (Aβ 42 ) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Aβ 42 -lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial. Objective To determine the efficacy, safety, and tolerability of Tarenflurbil. Design, Setting, and Patients A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted. Intervention Tarenflurbil, 800 mg, or placebo, administered twice a day. Main Outcome Measures Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale−Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies–activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification. Results Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, −0.9 to 1.1; P = .86 and −0.5 for ADCS-ADL; 95% CI, −1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The Tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections. Conclusion Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD. Trial Registration clinicaltrials.gov Identifier: NCT00105547

  • Effect of Tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial.
    JAMA, 2009
    Co-Authors: Robert C Green, Andrew P Beelen, Gordon Wilcock, Edward A Swabb, David A. Amato, Lon S Schneider, Kenton H Zavitz
    Abstract:

    CONTEXT Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial. OBJECTIVE To determine the efficacy, safety, and tolerability of Tarenflurbil. DESIGN, SETTING, AND PATIENTS A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted. INTERVENTION Tarenflurbil, 800 mg, or placebo, administered twice a day. MAIN OUTCOME MEASURES Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies-activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification. RESULTS Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, -0.9 to 1.1; P = .86 and -0.5 for ADCS-ADL; 95% CI, -1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The Tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections. CONCLUSION Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00105547.

Sonya Prescott - One of the best experts on this subject based on the ideXlab platform.

  • Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice.
    BMC Neuroscience, 2007
    Co-Authors: Thomas Kukar, Sonya Prescott, Jason L. Eriksen, Vallie M. Holloway, M. Paul Murphy, Todd E. Golde, Michelle M. Nicolle
    Abstract:

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (Tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice.

  • Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice
    BMC Neuroscience, 2007
    Co-Authors: Thomas Kukar, Sonya Prescott, Jason L. Eriksen, M. Paul Murphy, Todd E. Golde, Vallie Holloway, Michelle M. Nicolle
    Abstract:

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R -flurbiprofen (Tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R -flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R -flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R -flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R -flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its ability to selectively target Aβ42 production and improve cognitive impairments in transgenic APP mice, as well as promising data from a phase 2 human clinical trial, future studies are needed to investigate the utility of R -flurbiprofen as an AD therapeutic and its possible mechanisms of action.