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Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B

There is a lack of reliable, repeatable, and non-invasive clinical endpoints when investigating treatments for intellectual disability (ID). The aim of this study is to explore a novel approach towards developing new endpoints for neurodevelopmental disorders, in this case for ARID1B-related ID. In...

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Autores principales: Kruizinga, Matthijs D., Zuiker, Rob G.J.A., Sali, Elif, de Kam, Marieke L., Doll, Robert J., Groeneveld, Geert Jan, Santen, Gijs W.E., Cohen, Adam F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609730/
https://www.ncbi.nlm.nih.gov/pubmed/32462407
http://dx.doi.org/10.1007/s13311-020-00868-9
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author Kruizinga, Matthijs D.
Zuiker, Rob G.J.A.
Sali, Elif
de Kam, Marieke L.
Doll, Robert J.
Groeneveld, Geert Jan
Santen, Gijs W.E.
Cohen, Adam F.
author_facet Kruizinga, Matthijs D.
Zuiker, Rob G.J.A.
Sali, Elif
de Kam, Marieke L.
Doll, Robert J.
Groeneveld, Geert Jan
Santen, Gijs W.E.
Cohen, Adam F.
author_sort Kruizinga, Matthijs D.
collection PubMed
description There is a lack of reliable, repeatable, and non-invasive clinical endpoints when investigating treatments for intellectual disability (ID). The aim of this study is to explore a novel approach towards developing new endpoints for neurodevelopmental disorders, in this case for ARID1B-related ID. In this study, twelve subjects with ARID1B-related ID and twelve age-matched controls were included in this observational case–control study. Subjects performed a battery of non-invasive neurobehavioral and neurophysiological assessments on two study days. Test domains included cognition, executive functioning, and eye tracking. Furthermore, several electrophysiological assessments were performed. Subjects wore a smartwatch (Withings® Steel HR) for 6 days. Tests were systematically assessed regarding tolerability, variability, repeatability, difference with control group, and correlation with traditional endpoints. Animal fluency, adaptive tracking, body sway, and smooth pursuit eye movements were assessed as fit-for-purpose regarding all criteria, while physical activity, heart rate, and sleep parameters show promise as well. The event-related potential waveform of the passive oddball and visual evoked potential tasks showed discriminatory ability, but EEG assessments were perceived as extremely burdensome. This approach successfully identified fit-for-purpose candidate endpoints for ARID1B-related ID and possibly for other neurodevelopmental disorders. Next, results could be replicated in different ID populations or the assessments could be included as exploratory endpoint in interventional trials in ARID1B-related ID. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00868-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-76097302020-11-10 Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B Kruizinga, Matthijs D. Zuiker, Rob G.J.A. Sali, Elif de Kam, Marieke L. Doll, Robert J. Groeneveld, Geert Jan Santen, Gijs W.E. Cohen, Adam F. Neurotherapeutics Original Article There is a lack of reliable, repeatable, and non-invasive clinical endpoints when investigating treatments for intellectual disability (ID). The aim of this study is to explore a novel approach towards developing new endpoints for neurodevelopmental disorders, in this case for ARID1B-related ID. In this study, twelve subjects with ARID1B-related ID and twelve age-matched controls were included in this observational case–control study. Subjects performed a battery of non-invasive neurobehavioral and neurophysiological assessments on two study days. Test domains included cognition, executive functioning, and eye tracking. Furthermore, several electrophysiological assessments were performed. Subjects wore a smartwatch (Withings® Steel HR) for 6 days. Tests were systematically assessed regarding tolerability, variability, repeatability, difference with control group, and correlation with traditional endpoints. Animal fluency, adaptive tracking, body sway, and smooth pursuit eye movements were assessed as fit-for-purpose regarding all criteria, while physical activity, heart rate, and sleep parameters show promise as well. The event-related potential waveform of the passive oddball and visual evoked potential tasks showed discriminatory ability, but EEG assessments were perceived as extremely burdensome. This approach successfully identified fit-for-purpose candidate endpoints for ARID1B-related ID and possibly for other neurodevelopmental disorders. Next, results could be replicated in different ID populations or the assessments could be included as exploratory endpoint in interventional trials in ARID1B-related ID. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00868-9) contains supplementary material, which is available to authorized users. Springer International Publishing 2020-05-22 2020-07 /pmc/articles/PMC7609730/ /pubmed/32462407 http://dx.doi.org/10.1007/s13311-020-00868-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Kruizinga, Matthijs D.
Zuiker, Rob G.J.A.
Sali, Elif
de Kam, Marieke L.
Doll, Robert J.
Groeneveld, Geert Jan
Santen, Gijs W.E.
Cohen, Adam F.
Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B
title Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B
title_full Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B
title_fullStr Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B
title_full_unstemmed Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B
title_short Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B
title_sort finding suitable clinical endpoints for a potential treatment of a rare genetic disease: the case of arid1b
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609730/
https://www.ncbi.nlm.nih.gov/pubmed/32462407
http://dx.doi.org/10.1007/s13311-020-00868-9
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