The Experts below are selected from a list of 10431 Experts worldwide ranked by ideXlab platform

Ralf Reilmann - One of the best experts on this subject based on the ideXlab platform.

  • Activity Behaviour of Minipigs Transgenic for the Huntington Gene.
    Journal of Huntington's disease, 2019
    Co-Authors: Lorena Rieke, Verena Schuldenzucker, Robin Schubert, Michaela Fels, Nicole Kemper, Tamara Matheis, Benjamin Habbel, Ralf Reilmann
    Abstract:

    Background To increase the reliability of translating preclinical findings to humans, large animal models, such as the transgenic (tg) Libechov Minipig, were established. As Minipigs possess high genetic homology with humans and have similarities in anatomy, physiology and metabolism to humans, they are considered for studying neurodegenerative diseases longitudinally. Recently, sleep abnormalities and changes in circadian rhythm in Huntington's disease (HD) patients were acknowledged to present one of the early symptoms in HD. Objective The aim of the present study was to explore the activity behaviour of Libechov Minipigs and to investigate whether tgHD and wildtype (wt) Minipigs exhibit differences in activity behaviour. Furthermore, it was investigated whether activity assessments may serve as reliable endpoints for phenotyping Minipigs transgenic for the Huntington gene. Methods Activity behaviour of Minipigs was studied by video recording the stables twice a week over a total study period of five weeks for a cohort of five tgHD Minipigs and five wt Minipigs. Statistical analysis was performed using the linear mixed model. Once a week, the distances covered by two Minipigs in focus (tgHD, wt) were measured using the VideoMotionTracker® software. Results Libechov Minipigs showed a biphasic pattern of activity, spending most of the time inactive or grubbing in litter. Differences in activity behaviour (rooting, resting and standing) were detected between wt and tgHD Minipigs. The influence of the genotype on behavioural patterns was observed during circadian monitoring. TgHD Minipigs covered longer distances on average and during every 24 h observation period than wt Minipigs. Conclusion Activity behaviour may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Video recordings of behavioural patterns provide a non-invasive opportunity to capture potential disease signs. Phenotypic progression including the age of disease manifestation may be explored by documentation of circadian characteristics.

  • Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the Huntington Gene
    Journal of Huntington's disease, 2018
    Co-Authors: Lorena Rieke, Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Ralf Reilmann
    Abstract:

    Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington's disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt Minipigs. Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

  • B11 Vocalisation as a viable assessment for Minipigs transgenic for the huntington gene
    Models for HD, 2018
    Co-Authors: Lorena Rieke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Backround Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. Objective The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. Methods While conducting behavioural testing, vocalisation incidence was documented for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher’s Exact Test for group comparisons and McNemar’s Test for intra-visit differences between tgHD and wt Minipigs. Results Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation frequency across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1,5 years. Conclusion Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation. Acknowledgement This study was funded by the CHDI foundation.

  • C10 Behavioural phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neurology Neurosurgery & Psychiatry, 2016
    Co-Authors: Verena Schuldenzucker, Sarah Schramke, Robin Schubert, Jan Motlik, Lorena Rieke, Tamara Matheis, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioural phenotype of a transgenic (tg) HD Minipig model. Methods A group of tgHD and wildtype (wt) Libechov Minipigs (n = 36) was available for assessment with (1) a gait test using the GAITRite® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a startbox back and forth test and (5) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test-retest reliability, sensitivity and validity in assessing motor, cognitive and behavioural features of tg and wt Minipigs. Acknowledgement Funded by the CHDI Foundation.

Robin Schubert - One of the best experts on this subject based on the ideXlab platform.

  • Activity Behaviour of Minipigs Transgenic for the Huntington Gene.
    Journal of Huntington's disease, 2019
    Co-Authors: Lorena Rieke, Verena Schuldenzucker, Robin Schubert, Michaela Fels, Nicole Kemper, Tamara Matheis, Benjamin Habbel, Ralf Reilmann
    Abstract:

    Background To increase the reliability of translating preclinical findings to humans, large animal models, such as the transgenic (tg) Libechov Minipig, were established. As Minipigs possess high genetic homology with humans and have similarities in anatomy, physiology and metabolism to humans, they are considered for studying neurodegenerative diseases longitudinally. Recently, sleep abnormalities and changes in circadian rhythm in Huntington's disease (HD) patients were acknowledged to present one of the early symptoms in HD. Objective The aim of the present study was to explore the activity behaviour of Libechov Minipigs and to investigate whether tgHD and wildtype (wt) Minipigs exhibit differences in activity behaviour. Furthermore, it was investigated whether activity assessments may serve as reliable endpoints for phenotyping Minipigs transgenic for the Huntington gene. Methods Activity behaviour of Minipigs was studied by video recording the stables twice a week over a total study period of five weeks for a cohort of five tgHD Minipigs and five wt Minipigs. Statistical analysis was performed using the linear mixed model. Once a week, the distances covered by two Minipigs in focus (tgHD, wt) were measured using the VideoMotionTracker® software. Results Libechov Minipigs showed a biphasic pattern of activity, spending most of the time inactive or grubbing in litter. Differences in activity behaviour (rooting, resting and standing) were detected between wt and tgHD Minipigs. The influence of the genotype on behavioural patterns was observed during circadian monitoring. TgHD Minipigs covered longer distances on average and during every 24 h observation period than wt Minipigs. Conclusion Activity behaviour may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Video recordings of behavioural patterns provide a non-invasive opportunity to capture potential disease signs. Phenotypic progression including the age of disease manifestation may be explored by documentation of circadian characteristics.

  • Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the Huntington Gene
    Journal of Huntington's disease, 2018
    Co-Authors: Lorena Rieke, Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Ralf Reilmann
    Abstract:

    Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington's disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt Minipigs. Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

  • B11 Vocalisation as a viable assessment for Minipigs transgenic for the huntington gene
    Models for HD, 2018
    Co-Authors: Lorena Rieke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Backround Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. Objective The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. Methods While conducting behavioural testing, vocalisation incidence was documented for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher’s Exact Test for group comparisons and McNemar’s Test for intra-visit differences between tgHD and wt Minipigs. Results Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation frequency across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1,5 years. Conclusion Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation. Acknowledgement This study was funded by the CHDI foundation.

  • C10 Behavioural phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neurology Neurosurgery & Psychiatry, 2016
    Co-Authors: Verena Schuldenzucker, Sarah Schramke, Robin Schubert, Jan Motlik, Lorena Rieke, Tamara Matheis, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioural phenotype of a transgenic (tg) HD Minipig model. Methods A group of tgHD and wildtype (wt) Libechov Minipigs (n = 36) was available for assessment with (1) a gait test using the GAITRite® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a startbox back and forth test and (5) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test-retest reliability, sensitivity and validity in assessing motor, cognitive and behavioural features of tg and wt Minipigs. Acknowledgement Funded by the CHDI Foundation.

  • behavioral phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neuroscience Methods, 2016
    Co-Authors: Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Frauke Frank, M Wirsig, Stefanie Ott, Jan Motlik, Michaela Fels, Nicole Kemper, Eva Holzner
    Abstract:

    Abstract Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioral phenotype of a transgenic (tg) HD Minipig model. New methods A group of tgHD and wildtype (wt) Libechov Minipigs ( n  = 36) was available for assessment with (1) a gait test using the GAITRite ® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a color discrimination test, (5) a startbox back and forth test and (6) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Comparison with existing method(s) So far there are no established or validated assessments to test Minipigs in the domains described. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test–retest reliability, sensitivity and validity in assessing motor, cognitive and behavioral features of tg and wt Minipigs.

Verena Schuldenzucker - One of the best experts on this subject based on the ideXlab platform.

  • Activity Behaviour of Minipigs Transgenic for the Huntington Gene.
    Journal of Huntington's disease, 2019
    Co-Authors: Lorena Rieke, Verena Schuldenzucker, Robin Schubert, Michaela Fels, Nicole Kemper, Tamara Matheis, Benjamin Habbel, Ralf Reilmann
    Abstract:

    Background To increase the reliability of translating preclinical findings to humans, large animal models, such as the transgenic (tg) Libechov Minipig, were established. As Minipigs possess high genetic homology with humans and have similarities in anatomy, physiology and metabolism to humans, they are considered for studying neurodegenerative diseases longitudinally. Recently, sleep abnormalities and changes in circadian rhythm in Huntington's disease (HD) patients were acknowledged to present one of the early symptoms in HD. Objective The aim of the present study was to explore the activity behaviour of Libechov Minipigs and to investigate whether tgHD and wildtype (wt) Minipigs exhibit differences in activity behaviour. Furthermore, it was investigated whether activity assessments may serve as reliable endpoints for phenotyping Minipigs transgenic for the Huntington gene. Methods Activity behaviour of Minipigs was studied by video recording the stables twice a week over a total study period of five weeks for a cohort of five tgHD Minipigs and five wt Minipigs. Statistical analysis was performed using the linear mixed model. Once a week, the distances covered by two Minipigs in focus (tgHD, wt) were measured using the VideoMotionTracker® software. Results Libechov Minipigs showed a biphasic pattern of activity, spending most of the time inactive or grubbing in litter. Differences in activity behaviour (rooting, resting and standing) were detected between wt and tgHD Minipigs. The influence of the genotype on behavioural patterns was observed during circadian monitoring. TgHD Minipigs covered longer distances on average and during every 24 h observation period than wt Minipigs. Conclusion Activity behaviour may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Video recordings of behavioural patterns provide a non-invasive opportunity to capture potential disease signs. Phenotypic progression including the age of disease manifestation may be explored by documentation of circadian characteristics.

  • Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the Huntington Gene
    Journal of Huntington's disease, 2018
    Co-Authors: Lorena Rieke, Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Ralf Reilmann
    Abstract:

    Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington's disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt Minipigs. Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

  • B11 Vocalisation as a viable assessment for Minipigs transgenic for the huntington gene
    Models for HD, 2018
    Co-Authors: Lorena Rieke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Backround Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. Objective The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. Methods While conducting behavioural testing, vocalisation incidence was documented for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher’s Exact Test for group comparisons and McNemar’s Test for intra-visit differences between tgHD and wt Minipigs. Results Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation frequency across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1,5 years. Conclusion Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation. Acknowledgement This study was funded by the CHDI foundation.

  • C10 Behavioural phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neurology Neurosurgery & Psychiatry, 2016
    Co-Authors: Verena Schuldenzucker, Sarah Schramke, Robin Schubert, Jan Motlik, Lorena Rieke, Tamara Matheis, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioural phenotype of a transgenic (tg) HD Minipig model. Methods A group of tgHD and wildtype (wt) Libechov Minipigs (n = 36) was available for assessment with (1) a gait test using the GAITRite® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a startbox back and forth test and (5) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test-retest reliability, sensitivity and validity in assessing motor, cognitive and behavioural features of tg and wt Minipigs. Acknowledgement Funded by the CHDI Foundation.

  • behavioral phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neuroscience Methods, 2016
    Co-Authors: Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Frauke Frank, M Wirsig, Stefanie Ott, Jan Motlik, Michaela Fels, Nicole Kemper, Eva Holzner
    Abstract:

    Abstract Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioral phenotype of a transgenic (tg) HD Minipig model. New methods A group of tgHD and wildtype (wt) Libechov Minipigs ( n  = 36) was available for assessment with (1) a gait test using the GAITRite ® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a color discrimination test, (5) a startbox back and forth test and (6) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Comparison with existing method(s) So far there are no established or validated assessments to test Minipigs in the domains described. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test–retest reliability, sensitivity and validity in assessing motor, cognitive and behavioral features of tg and wt Minipigs.

Sarah Schramke - One of the best experts on this subject based on the ideXlab platform.

  • Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the Huntington Gene
    Journal of Huntington's disease, 2018
    Co-Authors: Lorena Rieke, Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Ralf Reilmann
    Abstract:

    Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington's disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt Minipigs. Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

  • C10 Behavioural phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neurology Neurosurgery & Psychiatry, 2016
    Co-Authors: Verena Schuldenzucker, Sarah Schramke, Robin Schubert, Jan Motlik, Lorena Rieke, Tamara Matheis, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioural phenotype of a transgenic (tg) HD Minipig model. Methods A group of tgHD and wildtype (wt) Libechov Minipigs (n = 36) was available for assessment with (1) a gait test using the GAITRite® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a startbox back and forth test and (5) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test-retest reliability, sensitivity and validity in assessing motor, cognitive and behavioural features of tg and wt Minipigs. Acknowledgement Funded by the CHDI Foundation.

  • behavioral phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neuroscience Methods, 2016
    Co-Authors: Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Frauke Frank, M Wirsig, Stefanie Ott, Jan Motlik, Michaela Fels, Nicole Kemper, Eva Holzner
    Abstract:

    Abstract Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioral phenotype of a transgenic (tg) HD Minipig model. New methods A group of tgHD and wildtype (wt) Libechov Minipigs ( n  = 36) was available for assessment with (1) a gait test using the GAITRite ® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a color discrimination test, (5) a startbox back and forth test and (6) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Comparison with existing method(s) So far there are no established or validated assessments to test Minipigs in the domains described. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test–retest reliability, sensitivity and validity in assessing motor, cognitive and behavioral features of tg and wt Minipigs.

  • C13 Mr-based Stereotaxic Standard Brain Atlas Of The LibĚchov Minipig
    Journal of Neurology Neurosurgery & Psychiatry, 2014
    Co-Authors: Robin Schubert, Sarah Schramke, Verena Schuldenzucker, Eva Holzner, F Frank, Nina Nagelmann, M Marcegaglia, Cornelius Faber, R Reilmann
    Abstract:

    Background In the TRACK TgHD Minipig study, we aim to investigate characteristics of the transgenic Libechov Minipig as a model for HD. Annual MRI scans are performed, including anatomical, spectroscopic and diffusion weighted imaging (DWI) sequences. To be able to perform quantitative analysis like the fractional anisotropy (FA), a standard brain is needed as target for registration of imaging data. To date, no standard brain atlas for the Libechov Minipig exists. Aims To provide a stereotaxic standard brain atlas of the Libechov Minipig that serves primarily as target for registration of diffusion weighted MR images. Methods/techniques 36 T1 weighted, sagittal acquired MRI volumes of 32 Libechov Minipigs were transformed into a common coordinate system and skull-stripped with a BET algorithm. The extracted brains were coregistered with a 12 parameter affine registration within multiple iteration steps. To define the anatomical structures, an available MR-based statistical atlas of the Gottinger Minipig brain was registered on the averaged standard brain and the different regions were carefully compared. Binary maps of 34 segmented brain structures were created. The T1 weighted images were acquired with a 3T Philips Achieva scanner. Results/outcome T1-weighted 3D volumes of brains of 32 Minipigs have successfully been acquired. A standard brain template could be created as target for registration. The mapping of structural regions to create a brain atlas is still in progress and will first be presented at the EHDN meeting. Conclusions Most quantitative analysis methods for MR images require registration of the images to a standard volume. Such templates already exist for several species, but not for the Libechov Minipig. The resulting brain template serves as registration target for diffusion weighted MR images and is the first step in creating a Libechov Minipig FA template for quantitative analysis of cross sectional and longitudinal DWI data. This study was supported by a grant of the CHDI Foundation.

  • C19 Track Tghd Minipigs – A Discrimination Test As Part Of An Assessment Battery For Tghd Minipigs
    Journal of Neurology Neurosurgery & Psychiatry, 2014
    Co-Authors: Sarah Schramke, Verena Schuldenzucker, Robin Schubert, M Wirsig, Eva Holzner, F Frank, M Marcegaglia, S Ott, R Reilmann
    Abstract:

    Background The TRACK tgHD Minipig study aims to evaluate the potential of the Libechov tgHD Minipig model for pre-clinical studies by studying the phenotype of these animals. Established tests for assessing different domains of possible phenotype manifestation in Minipigs are lacking. The “Discrimination Test” introduced here is thought to primarily target cognitive dysfunction. Aim To assess the feasibility and tolerability of the application of the “Discrimination Test” in Minipigs and explore the tgHD Minipigs’ performance compared with that of wildtype (wt) Minipigs. Methods/techniques Thirty-two Minipigs – 18 wt and 14 tg (with an N-terminal fragment of the huntingtin gene coding for 548aa with 124Q) – were included in the study. The Minipigs were housed in six mixed groups (wt and tg) at the animal facility of the University of Muenster, Germany. The “Discrimination Test” was performed using a special setup. During initial training, the Minipigs learnt to leave a startbox (SB A), enter a walkway, open a blue plastic box (bB) as opposed to red and yellow box (rB/yB), and return to SB A. The boxes’ position was changed clockwise in subsequent runs. During testing 1, time to leave SB A and open bB, and time to leave bB and return to SB A was recorded and a score was given based on attempts to open and/or investigate bB and/or rB and yB. During testing 2, yB had to be opened instead of bB and yB (intradimensional shift). Each pig completes training, testing 1 and testing 2 biannually. Results/outcome The animals show a good tolerance of the method. Cross sectional and longitudinal data analysis is in progress using SPSS 22.0. Conclusion The data collected to date shows that implementation of the “Discrimination Test” is feasible and well tolerated. It is hypothesised that performance of the test is impaired in tgHD Minipigs compared to controls. We expect to report first between group comparisons at the meeting. Acknowledgement This study was funded by the CHDI foundation.

Jan Motlik - One of the best experts on this subject based on the ideXlab platform.

  • Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the Huntington Gene
    Journal of Huntington's disease, 2018
    Co-Authors: Lorena Rieke, Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Ralf Reilmann
    Abstract:

    Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington's disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt Minipigs. Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

  • B11 Vocalisation as a viable assessment for Minipigs transgenic for the huntington gene
    Models for HD, 2018
    Co-Authors: Lorena Rieke, Verena Schuldenzucker, Robin Schubert, Jan Motlik, Michaela Fels, Nicole Kemper, Tamara Matheis, Lisa M. Muratori, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Backround Large animal models, such as the transgenic (tg) Huntington disease (HD) Minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in Minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. Objective The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping Minipigs transgenic for Huntington disease (tgHD) and whether tgHD Minipigs reveal changes in this domain compared to wildtype (wt) Minipigs. Methods While conducting behavioural testing, vocalisation incidence was documented for a cohort of 14 tgHD and 18 wt Minipigs. Statistical analyses were performed using Fisher’s Exact Test for group comparisons and McNemar’s Test for intra-visit differences between tgHD and wt Minipigs. Results Vocalisation can easily be documented during phenotyping assessments of Minipigs. Differences in vocalisation frequency across behavioural conditions were detected between tgHD and wt Minipigs. Influence of the genotype on vocalisation was detectable during a period of 1,5 years. Conclusion Vocalisation may be a viable marker for phenotyping Minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation. Acknowledgement This study was funded by the CHDI foundation.

  • C10 Behavioural phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neurology Neurosurgery & Psychiatry, 2016
    Co-Authors: Verena Schuldenzucker, Sarah Schramke, Robin Schubert, Jan Motlik, Lorena Rieke, Tamara Matheis, Frauke Freisfeld, Ralf Reilmann
    Abstract:

    Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioural phenotype of a transgenic (tg) HD Minipig model. Methods A group of tgHD and wildtype (wt) Libechov Minipigs (n = 36) was available for assessment with (1) a gait test using the GAITRite® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a startbox back and forth test and (5) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test-retest reliability, sensitivity and validity in assessing motor, cognitive and behavioural features of tg and wt Minipigs. Acknowledgement Funded by the CHDI Foundation.

  • behavioral phenotyping of Minipigs transgenic for the huntington gene
    Journal of Neuroscience Methods, 2016
    Co-Authors: Sarah Schramke, Verena Schuldenzucker, Robin Schubert, Frauke Frank, M Wirsig, Stefanie Ott, Jan Motlik, Michaela Fels, Nicole Kemper, Eva Holzner
    Abstract:

    Abstract Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioral phenotype of a transgenic (tg) HD Minipig model. New methods A group of tgHD and wildtype (wt) Libechov Minipigs ( n  = 36) was available for assessment with (1) a gait test using the GAITRite ® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a color discrimination test, (5) a startbox back and forth test and (6) a dominance test. Performance of all tests and definition of measures obtained is presented. Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt Minipigs assessed, but low variability within and between groups. Comparison with existing method(s) So far there are no established or validated assessments to test Minipigs in the domains described. Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test–retest reliability, sensitivity and validity in assessing motor, cognitive and behavioral features of tg and wt Minipigs.

  • expression of huntingtons disease markers in the cornea of Minipig transgenic for the human mutated huntingtin
    Acta Ophthalmologica, 2013
    Co-Authors: T Ardan, S Juhas, Jan Motlik
    Abstract:

    Purpose Huntingtons disease (HD) is a neurodegenerative disorder that is caused by an expansion of a polyglutamine (polyQ) domain in the protein of huntingtin (htt). PolyQ expansion above 35–40 results in disease associated with htt aggregation into inclusion bodies. The recent studies have shown that the illness arises not only in neurons, but also in non-neuronal cells. Purpose of this study was to investigate the expression of selected HD markers (on htt and their aggregates, ferritin and ubiquitin) in corneas of Minipig transgenic for the human mutated huntingtin and compare them with corneas of wild type (WT) Minipig. Methods In this study we used WT Minipigs and Minipigs transgenic for N-terminal part of the human mutated huntingtin (both F2 generation, age 24 months). HD markers were examined on cryostat sections immunohistochemically by using the following primary antibodies: anti-polyglutamines, anti-polyglutamine-expansion diseases marker, MW8 marker, anti-ferritin and anti-ubiguitin. Results Immunohistochemical examination on huntingtin demonstrated the increased expression of this protein in corneal epithelium and keratocytes of transgenic Minipig in comparison with wild type cornea. The expression of ferritin detected in epithelial cells was very low in both studied corneas without significant difference between them. No nuclear inclusions or ubiquitous proteins were found in the cornea of transgenic Minipig. Conclusion This study showed that preclinical (silent) stages of HD are characterized by an elevated level of mutagenic huntingtin without formation of nuclear inclusions and ubiquitination of proteins. Supported by CHDI Foundation (A-5378 and A-5379), TA01011466, CZ.1.05./2.1.00/03.0124 and RVO: 67985904.