Human brain development consists of a series of complex spatiotemporal processes that if disturbed by chemical exposure causes irreversible impairments of the nervous system. To evaluate a chemical disturbance in an alternative assay, the concept evolved that the complex procedure of brain development can be disassembled into several neurodevelopmental endpoints which can be represented by a combination of different alternative assays. In this review article, we provide a scientific rationale for the neurodevelopmental endpoints that are currently chosen to establish assays with human stem/and progenitor cells. Assays covering these major neurodevelopmental endpoints are thought to assemble as building blocks of a DNT testing battery.
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http://dx.doi.org/10.1093/toxsci/kfy175 | DOI Listing |
Value Health
December 2024
FamilieSCN2A Foundation, E. Longmeadow, MA, USA; Decoding Developmental Epilepsies - DEE-P Connections; Washington, DC, USA; Northwestern Feinberg School of Medicine, Dept. Neurology, Chicago, IL, USA.
Objectives: For individuals living with rare neurodevelopmental disorders, especially those who are at the most severe end of the spectrum, standardized outcome measures may lack the sensitivity to capture small but meaningful changes. Personalized endpoints such as Goal Attainment Scaling (GAS) allow the assessment of treatment response across variable baseline states and disease manifestations and thus provide a highly sensitive measure of efficacy. The current study tested the feasibility of using GAS in rare SCN2A-associated developmental and epileptic encephalopathy (SCN2A-DEE).
View Article and Find Full Text PDFPsychopharmacology (Berl)
December 2024
Medical Research Group of Egypt, Negida Academy, Arlington, MA, USA.
Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder. It is one of the most common mental disorders in youth worldwide characterized by persistent overactivity and impulsivity/inattention symptoms associated with social and academic impairment. dasotraline has been suggested to play a pivotal role as a serotonin, norepinephrine, and dopamine reuptake inhibitor.
View Article and Find Full Text PDFOrphanet J Rare Dis
December 2024
Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
Background: This study evaluated the clinical characteristics of neuronal ceroid lipofuscinosis type 7 or CLN7 disease spectrum to characterize the clinical, electrophysiologic and neuroimaging phenotypes.
Methods: We performed a single-center cross sectional data collection along with retrospective medical chart review in patients with a genetic diagnosis of CLN7. This study received ethical approval by the University of Texas Southwestern Medical Center Institutional Review Board.
Curr Neurol Neurosci Rep
December 2024
Kennedy Krieger Institute and Department of Psychiatry & Behavioral Sciences-Child Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Purpose Of The Review: Preclinical and clinical evidence support the notion that neurodevelopmental disorders (NDDs) are synaptic disorders, characterized by excitatory-inhibitory imbalance. Despite this, NDD drug development programs targeting glutamate or gamma-aminobutyric acid (GABA) receptors have been largely unsuccessful. Nonetheless, recent drug trials in Rett syndrome (RTT), fragile X syndrome (FXS), and other NDDs targeting other mechanisms have met their endpoints.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
October 2024
Department of Public Health and Pediatric Sciences, Section of Child and Adolescent Neuropsychiatry, University of Turin, Turin, Italy.
Part I of this systematic review summarized the state-of-the-art of pediatric psychopharmacology for Autism Spectrum Disorder (ASD), a severe and lifelong neurodevelopmental disorder. The purpose of this Part II follow-up article is to provide a systematic overview of the experimental psychopharmacology of ASD. To this aim, we have first identified in the Clinicaltrials.
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