Finding suitable clinical endpoints for a potential treatment of a rare genetic disease
| العنوان: | Finding suitable clinical endpoints for a potential treatment of a rare genetic disease |
|---|---|
| المؤلفون: | Geert Jan Groeneveld, Adam F. Cohen, Gijs W. E. Santen, Matthijs D. Kruizinga, Robert Doll, Rob Zuiker, Marieke L. de Kam, Elif Sali |
| المصدر: | Neurotherapeutics Neurotherapeutics, 17, 1300-1310. SPRINGER |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, medicine.medical_specialty, Neurology, Adolescent, Endpoint Determination, Electroencephalography, 03 medical and health sciences, Executive Function, Young Adult, 0302 clinical medicine, Physical medicine and rehabilitation, Cognition, Intellectual Disability, Intellectual disability, medicine, Clinical endpoint, Animals, Humans, Pharmacology (medical), Child, Pharmacology, Eye tracking, medicine.diagnostic_test, business.industry, Genetic Variation, medicine.disease, Endpoint, ARID1B, DNA-Binding Proteins, Electrophysiology, 030104 developmental biology, Tolerability, Case-Control Studies, Child, Preschool, Evoked Potentials, Visual, Observational study, Female, Original Article, Neurology (clinical), business, Executive functioning, 030217 neurology & neurosurgery, Photic Stimulation, Biomarkers, Transcription Factors |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97677620187efa274fe2c598779a399bTest https://hdl.handle.net/1887/3181370Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....97677620187efa274fe2c598779a399b |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |