Can genetic therapy help kids with Angelman syndrome overcome seizures?

(University of North Carolina Health Care) Angelman syndrome is a genetic disease with no cure. Children grow up with severe intellectual disabilities and a range of other problems, arguably the worst of which are epileptic seizures. Now scientists at the UNC School of Medicine have found evidence that genetic therapy may prevent the enhanced seizure susceptibility.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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Publication date: Available online 21 February 2020Source: NeuroscienceAuthor(s): Diana C. Rotaru, Edwin J. Mientjes, Ype ElgersmaAbstractThe UBE3A gene is part of the chromosome 15q11-q13 region that is frequently deleted or duplicated, leading to several neurodevelopmental disorders. Angelman syndrome (AS) is caused by the absence of functional maternally derived UBE3A protein, while the paternal UBE3A gene is present but silenced specifically in neurons. Patients with AS present with severe neurodevelopmental delay, with pronounced motor deficits, absence of speech, intellectual disability, epilepsy, and sleep problems....
Source: Neuroscience - Category: Neuroscience Source Type: research
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, lack of speech, ataxia, EEG abnormalities, and epilepsy. Seizures in individuals with AS are common, debilitating, and often drug resistant. Thus, there is an unmet need for better treatment options. Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, has shown antiseizure activity and behavioral benefits in preclinical and clinical studies for some disorders associated with epilepsy, suggesting that the same could be true for AS. Here, we show that acute CBD (100 mg/kg) treatment attenuated hyperthermia- and ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
ConclusionClinical work ‐up of an individual with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor should prompt methylation studies to rule out mAS. We expand the phenotypic spectrum of AS to include features that overlap with Prader‐Willi such as hyperphagia.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
Conclusion The findings of this study suggest that buspirone may be effective for the amelioration of behaviors related to anxiety in patients with AS, and well tolerated. Limitations include the open-label nature of these treatments, the small sample size and the absence of a control group.
Source: Psychiatric Genetics - Category: Genetics & Stem Cells Tags: ORIGINAL ARTICLES Source Type: research
ConclusionsOur study provides a useful tool for preclinical drug testing to identify treatments for Angelman syndrome. Since the phenotypes are observed in several independently derivedUbe3a lines, the test battery can also be employed to investigate the effect of specificUbe3a mutations on these phenotypes.
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsWe demonstrate two quantitative readouts of dysregulated sleep composition in children with AS —gamma coherence and spindles—and describe how functional connectivity patterns may be disrupted during wakefulness. Quantitative EEG phenotypes have potential as biomarkers and readouts of target engagement for future clinical trials and provide clues into how neural circuits are dysregulated i n children with AS.
Source: Molecular Autism - Category: Molecular Biology Source Type: research
Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, expressive speech impairment, movement disorder, epilepsy, and a happy demeanor. Children with AS are frequently reported to be poor feeders during infancy and as having gastrointestinal issues such as constipation, reflux, and abnormal food related behaviors throughout their lifetime. To assess the prevalence of gastrointestinal disorders in individuals with AS, we retrospectively analyzed medical records of 120 individuals seen at the Angelman Syndrome Clinic at Massachusetts General Hospital and 43 individuals seen at the Univers...
Source: American Journal of Medical Genetics Part A - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
Conclusions:The high yield (17.4%) of pathogenic or likely pathogenic CNVs in patients with epilepsy and ID of undefined etiology reinforces the role of CNVs in this patient group and the need for routine SNP array studies in the clinic. CNVs can be used to identify novel candidate epilepsy genes although identification of additional cases with mutations in these genes and functional analyses are required to confirm their role in epilepsy.Study Supported by: The Ontario Brain InstituteDisclosure: Dr. Borlot has nothing to disclose. Dr. Bassett has nothing to disclose. Dr. Regan has nothing to disclose. Dr. Stavropoulos has...
Source: Neurology - Category: Neurology Authors: Tags: Epilepsy and Clinical Neurophysiology: Genetics Source Type: research
Conclusion: Children with AS have high rates of incontinence. Many adults are still affected by NE, DUI, or even FI. Screening, assessment, and treatment of incontinence in individuals with AS are recommended.What is Known:•Incontinence in persons with Angelman syndrome (AS) is associated with younger age, lower level of adaptive functioning, and epilepsy.What is New:•Children and teens with AS are at special risk for incontinence, but older persons are also affected.•Comorbid epilepsy is significantly associated not only with nocturnal enuresis (NE) but also with daytime urinary incontinence (DUI). Underlyi...
Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
Conclusion Epilepsy is very common in patients with AS, especially in patients with a deletion. Postural muscle tone loss and collapsing during outbursts of laughter were seen in patients with a deletion only.
Source: Research in Developmental Disabilities - Category: Disability Source Type: research
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