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Title:
Development of Antisense Oligonucleotide Gapmers for the Treatment of Dyslipidemia and Lipodystrophy | SpringerLink
Description:
Although technological advances in molecular genetics over the last few decades have greatly expedited the identification of mutations in many genetic diseases, the translation of the genetic mechanisms into a clinical setting has been quite challenging, with a...
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/news-releases/news-release-details/akcea vldl-apolipoprotein c-iii kinetics org/rare-diseases/familial-partial-lipodystrophy/ /~/media/kynamro/files/kynamro-pi ionis-announce-approval-waylivrar-volanesorsen month download article/chapter modern anti-dyslipidemic arsenal fda-approved oligonucleotide therapies splice-switching antisense oligonucleotide plasma apolipoprotein c-iii short-term triglyceride lowering vivo pk/pd relationships low-density lipoprotein cholesterol apoc-ii mimetic peptide cell-penetrating peptides human neurodegenerative diseases peptide-conjugated morpholinos lipid-mediated diseases ldl cholesterol concentrations antisense-mediated lowering antisense oligonucleotide gapmers short-term administration apolipoprotein c-iii rna targeting therapeutics systemic brain delivery garrett cumming research duchenne muscular dystrophy privacy choices/manage cookies antisense oligonucleotide therapies ps backbone flanked blom dj kastelein jj systemic multiexon skipping device instant download cholesterol-lowering treatment apolipoprotein c-ii high-dose atorvastatin human apoc3 confers ionis announce approval increases antithrombin iii antisense oligonucleotide inhibition familial partial lipodystrophy injection prescribing information editor information editors drug administration usual-dose simvastatin chan dc aace consensus statement heterozygous familial hypercholesterolemia spinal muscular atrophy

Questions {❓}

Chan DC, Chen MM, Ooi EM et al (2008) An ABC of apolipoprotein C-III: a clinically useful new cardiovascular risk factor?

Schema {🗺️}

ScholarlyArticle:
      headline:Development of Antisense Oligonucleotide Gapmers for the Treatment of Dyslipidemia and Lipodystrophy
      pageEnd:85
      pageStart:69
      image:https://media.springernature.com/w153/springer-static/cover/book/978-1-0716-0771-8.jpg
      genre:
         Springer Protocols
      isPartOf:
         name:Gapmers
         isbn:
            978-1-0716-0771-8
            978-1-0716-0770-1
         type:Book
      publisher:
         name:Springer US
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Tejal Aslesh
            affiliation:
                  name:University of Alberta
                  address:
                     name:Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
                     type:PostalAddress
                  type:Organization
                  name:University of Alberta
                  address:
                     name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Toshifumi Yokota
            affiliation:
                  name:University of Alberta
                  address:
                     name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
                     type:PostalAddress
                  type:Organization
                  name:The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair
                  address:
                     name:The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, Edmonton, Canada
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      keywords:2′-O-methoxyethyl (MOE), Low-density lipoprotein (LDL), Apolipoprotein B-100 (ApoB-100), Homozygous familial hypercholesterolemia, Hypertriglyceridemia, Familial chylomicronemia, Familial partial lipodystrophy, Nusinersen (brand name Spinraza), Eteplirsen (brand name Exondys 51), Cardiovascular diseases (CVD)
      description:Although technological advances in molecular genetics over the last few decades have greatly expedited the identification of mutations in many genetic diseases, the translation of the genetic mechanisms into a clinical setting has been quite challenging, with a minimum number of effective treatments available. The advancements in antisense therapy have revolutionized the field of neuromuscular disorders as well as lipid-mediated diseases. With the approval of splice-switching antisense oligonucleotide (AO) therapy for nusinersen and eteplirsen for the treatment of spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD), several modified AOs are now being evaluated in clinical trials for the treatment of a number of disorders. In order to activate RNase H-mediated cleavage of the target mRNA, as well as to increase the binding affinity and specificity, gapmer AOs are designed that have a PS backbone flanked with the modified AOs on both sides. Mipomersen (trade name Kynamro), a 2′-O-methoxyethyl (MOE) gapmer, was approved by the Food and Drug Administration (FDA) for the treatment of homozygous familial hypercholesterolemia (HoFH) in 2013. Volanesorsen, another 20-mer MOE gapmer has shown to be successful in lowering the levels of triglycerides (TGs) in several lipid disorders and has received conditional approval in the European Union for the treatment of Familial chylomicronemia syndrome (FCS) in May 2019 following successful results from phase II/III clinical trials. This chapter focuses on the clinical applications of gapmer AOs for genetic dyslipidemia and lipodystrophy.
      datePublished:2020
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         978-1-0716-0770-1
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      name:University of Alberta
      address:
         name:Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
         type:PostalAddress
      name:University of Alberta
      address:
         name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
         type:PostalAddress
      name:University of Alberta
      address:
         name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
         type:PostalAddress
      name:The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair
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      name:Tejal Aslesh
      affiliation:
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            address:
               name:Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
               type:PostalAddress
            type:Organization
            name:University of Alberta
            address:
               name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
               type:PostalAddress
            type:Organization
      name:Toshifumi Yokota
      affiliation:
            name:University of Alberta
            address:
               name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
               type:PostalAddress
            type:Organization
            name:The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair
            address:
               name:The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, Edmonton, Canada
               type:PostalAddress
            type:Organization
      email:[email protected]
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      name:Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
      name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
      name:Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
      name:The Friends of Garrett Cumming Research and Muscular Dystrophy Canada HM Toupin Neurological Science Research Chair, Edmonton, Canada
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