Stem cells help researchers identify neuronal defects causing Angelman syndrome

Researchers have used stem cells derived from patients with Angelman syndrome to identify the underlying neuronal defects that cause the rare neurogenetic disorder, an important step in the ongoing search for potential treatments for Angelman and a possible cure.
Source: ScienceDaily Headlines - Category: Science Source Type: news

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In the past few blogs, I've been discussing the recent publication of my book,Evolution ’s Clinical Guidebook: Translating Ancient Genes Into Precision Medicine. The premise of this book is that modern medicine is based on an understanding of evolutionary processes. Evolution shows us the relationships between the subdisciplines of medicine that benefit directly from Precision Medicine (i.e., pathology, microbiology, clinical genetics, pharmacology, and bioinformatics). In Evolution's Clinical Guidebook, all of these diverse fields are brought together, under the subject of evolution. To illustrate, I have listed bel...
Source: Specified Life - Category: Information Technology Tags: bioinformatics clinical genetics evo-devo evolution precision medicine rare disease Source Type: blogs
Publication date: Available online 10 December 2018Source: Stem Cell ResearchAuthor(s): Takeshi Niki, Keiko Imamura, Takako Enami, Masako Kinoshita, Haruhisa InoueAbstractAngelman syndrome is a rare neurodevelopmental disorder caused by the loss of function of the maternally expressed E3 ubiquitin ligase UBE3A. We established human induced pluripotent stem cells (iPSCs) from an Angelman syndrome patient with the deletion of maternal 15q11.2-13 including UBE3A gene. The generated iPSC line showed pluripotency markers and the ability of in vitro differentiation into three-germ layer. FISH analysis and methylation-specific PC...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Abstract NSI-189 Phosphate, (4-benzylpiperazin-1-yl)-[2-(3-methyl-butylamino)pyridin-3-yl] methanone is a new chemical entity under development for the treatment of MDD, based upon preclinical data demonstrating stimulation of neurogenesis of human hippocampus-derived neural stem cells in vitro and in mouse hippocampus in vivo. Previous studies have examined the tolerability and efficacy of NSI-189 for treating major depressive disorder (MDD). NSI-189 has shown significant potential as a treatment for MDD, with concurrent improvement of a cognition scale in a small double-blind, placebo-controlled study. The curre...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research
Publication date: Available online 24 September 2018Source: Stem Cell ResearchAuthor(s): Anika Neureiter, Björn Brändl, Michaela Hiber, Rashmi Tandon, Franz-Josef Müller, Laura SteenpassAbstractAngelman syndrome (AS) is a neurodevelopmental disorder with leading symptoms of happy demeanor, intellectual disability, ataxia and seizures. AS can be caused by genetic and epigenetic aberrations, resulting in the absence of functional UBE3A protein in the brain. UBE3A is an imprinted gene, which is, in neurons of the brain, expressed exclusively from maternal chromosome 15. The generated iPSC line was derived from ...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
ConclusionsWe provide pharmacological profiles of indenoisoquinoline-derived Top1 inhibitors as paternalUbe3a unsilencers. All 13 tested compounds were effective at unsilencing paternalUbe3a, although with variable efficacy and potency. Indotecan (LMP400) demonstrated a better pharmacological profile ofUbe3a unsilencing compared to our previous lead compound, topotecan. Taken together, indotecan and its structural analogues are potential AS therapeutics whose translational potential in AS treatment should be further assessed.
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsFinding a significant increase in bothHERC2 andUBE3A in Dup15q neurons and significant decrease in these two genes in AS deletion neurons may explain differences between AS deletion class andUBE3A specific classes of AS mutation whereHERC2 is expressed at normal levels. Also, we identified an enrichment for FOXO1-regulated transcripts in Dup15q neurons including ASD-associated genesEHPB2 andRORA indicating a possible connection between this syndromic form of ASD and idiopathic cases.
Source: Molecular Autism - Category: Molecular Biology Source Type: research
In January, 2018, Academic Press published my bookPrecision Medicine and the Reinvention of Human Disease. This book has an excellent " look inside " at itsGoogle book site, which includes the Table of Contents. In addition, I thought it might be helpful to see the topics listed in the Book's index. Note that page numbers followed by f indicate figures, t indicate tables, and ge indicate glossary terms.AAbandonware, 270, 310geAb initio, 34, 48ge, 108geABL (abelson leukemia) gene, 28, 58ge, 95 –97Absidia corymbifera, 218Acanthameoba, 213Acanthosis nigricans, 144geAchondroplasia, 74, 143ge, 354geAcne, 54ge, 1...
Source: Specified Life - Category: Information Technology Tags: index jules berman jules j berman precision medicine Source Type: blogs
Authors: Riemens RJM, Soares ES, Esteller M, Delgado-Morales R Abstract Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized mode...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
CpG islands (CGIs) are primarily promoter-associated genomic regions and are mostly unmethylated within highly methylated mammalian genomes. The mechanisms by which CGIs are protected from de novo methylation remain elusive. Here we show that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation. By targeting the DNA mismatch repair gene MLH1 CGI, we could generate a PSC model of a cancer-related epimutation. Furthermore, we succes...
Source: ScienceNOW - Category: Science Authors: Tags: Molecular Biology r-articles Source Type: news
Contributors : Norra Urraca ; Quynh T Tran ; Grant T Belgard ; Rawaha Memon ; Sarita Goorha ; Colleen Valdez ; Silvia Sanchez ; Juanma Ramirez ; Martin Donaldson ; Dave Bridges ; Lawrence T ReiterSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensA major problem in studying neurogenetic syndromes is obtaining live neurons from people with these disorders. We have taken a novel approach to studying gene expression in neurons from Angelman or Dup15q syndrome subjects using dental pulp stem cells (DPSC). Shed teeth were collected to generate DPSC lines from 3 AS deletion, 3 15q Duplication ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
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