Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/27841
Title: Natural History Studies and Clinical Trial Readiness for Genetic Developmental and Epileptic Encephalopathies.
Austin Authors: Palmer, Elizabeth E;Howell, Katherine;Scheffer, Ingrid E 
Affiliation: Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia
Epilepsy Research Centre
Sydney Children's Hospital Network, Sydney, NSW, Australia
School of Women's and Children's Health, UNSW, Sydney, NSW, Australia
Department of Neurology, Royal Children's Hospital, Parkville, VIC, Australia
Murdoch Children's Research Institute, Melbourne, VIC, Australia
Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
Issue Date: 2021
Date: 2021-10-27
Publication information: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2021; 18(3): 1432-1444
Abstract: The developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies. They usually begin in infancy or childhood with drug-resistant seizures, epileptiform EEG patterns, developmental slowing or regression, and cognitive impairment. DEEs have a high mortality and profound morbidity; comorbidities are common including autism spectrum disorders. With advances in genetic sequencing, over 400 genes have been implicated in DEEs, with a genetic cause now identified in over 50% patients. Each genetic DEE typically has a broad genotypic-phenotypic spectrum, based on the underlying pathophysiology. There is a pressing need to improve health outcomes by developing novel targeted therapies for specific genetic DEE phenotypes that not only improve seizure control, but also developmental outcomes and comorbidities. Clinical trial readiness relies firstly on a deep understanding of phenotype-genotype correlation and evolution of a condition over time, in order to select appropriate patients for clinical trials. Understanding the natural history of the disorder informs assessment of treatment efficacy in terms of both clinical outcome and biomarker utility. Natural history studies (NHS) provide a high quality, integrated, comprehensive approach to understanding a complex disease and underpin clinical trial design for novel therapies. NHS are pre-planned observational studies designed to track the course of a disease and identify demographic, genetic, environmental, and other variables, including biomarkers, that correlate with the disease's evolution and outcomes. Due to the rarity of individual genetic DEEs, appropriately funded high-quality DEE NHS will be required, with sustainable frameworks and equitable access to affected individuals globally.
URI: https://ahro.austin.org.au/austinjspui/handle/1/27841
DOI: 10.1007/s13311-021-01133-3
Journal: NeuroTherapeutics
PubMed URL: 34708325
Type: Journal Article
Subjects: Biomarkers
Clinical outcome assessments
Clinical trials
Developmental and epileptic encephalopathies
Epilepsy
Natural history studies
Appears in Collections:Journal articles

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