Annemieke Aartsma-Rus

Summary

Affiliation: Leiden University Medical Center
Country: The Netherlands

Publications

  1. ncbi request reprint Antisense-mediated modulation of splicing: therapeutic implications for Duchenne muscular dystrophy
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    RNA Biol 7:453-61. 2010
  2. pmc The effects of low levels of dystrophin on mouse muscle function and pathology
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 7:e31937. 2012
  3. doi request reprint DMD transcript imbalance determines dystrophin levels
    Pietro Spitali
    1Department of Human Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    FASEB J 27:4909-16. 2013
  4. pmc Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double-knockout mice
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    FASEB J 27:2484-95. 2013
  5. doi request reprint Innovating therapies for muscle diseases
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Electronic address
    Handb Clin Neurol 113:1497-501. 2013
  6. doi request reprint Overview on AON design
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Methods Mol Biol 867:117-29. 2012
  7. doi request reprint Overview on DMD exon skipping
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Methods Mol Biol 867:97-116. 2012
  8. pmc Therapeutic exon skipping for dysferlinopathies?
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 18:889-94. 2010
  9. ncbi request reprint Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule
    Annemieke Aartsma-Rus
    Leiden University Medical Center, Department of Human Genetics, P O Box 9600, 2300 RC Leiden, The Netherlands
    Muscle Nerve 34:135-44. 2006
  10. pmc Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Mol Ther 17:548-53. 2009

Collaborators

Detail Information

Publications56

  1. ncbi request reprint Antisense-mediated modulation of splicing: therapeutic implications for Duchenne muscular dystrophy
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    RNA Biol 7:453-61. 2010
    ....
  2. pmc The effects of low levels of dystrophin on mouse muscle function and pathology
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 7:e31937. 2012
    ..Based on these findings, we conclude that while even dystrophin levels below 15% can improve pathology and performance, levels of >20% are needed to fully protect muscle fibers from exercise-induced damage...
  3. doi request reprint DMD transcript imbalance determines dystrophin levels
    Pietro Spitali
    1Department of Human Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    FASEB J 27:4909-16. 2013
    ..We suggest that the availability of the complete transcript is a key factor to determine protein abundance and thus will influence the outcome of mRNA-targeting therapies...
  4. pmc Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double-knockout mice
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    FASEB J 27:2484-95. 2013
    ..These findings suggest that the dystrophin levels needed to benefit vitality and functioning of patients with DMD might be lower than those needed for full protection against muscle damage...
  5. doi request reprint Innovating therapies for muscle diseases
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Electronic address
    Handb Clin Neurol 113:1497-501. 2013
    ..Although none of the proposed strategies has yet proven to be of therapeutic value in patients, it is reasonable to expect that clinical efficacy will soon be demonstrated for some of the more advanced approaches...
  6. doi request reprint Overview on AON design
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Methods Mol Biol 867:117-29. 2012
    ..This allows retrospective analysis of effective and ineffective AONs to obtain guidelines to optimize future AON design...
  7. doi request reprint Overview on DMD exon skipping
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Methods Mol Biol 867:97-116. 2012
    ..Finally, an overview of clinical trials is given and outstanding questions and hurdles are discussed...
  8. pmc Therapeutic exon skipping for dysferlinopathies?
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 18:889-94. 2010
    ..We also show that DYSF exon skipping seems to be as straightforward as DMD exon skipping, as AONs to induce efficient skipping of four DYSF exons were readily identified...
  9. ncbi request reprint Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule
    Annemieke Aartsma-Rus
    Leiden University Medical Center, Department of Human Genetics, P O Box 9600, 2300 RC Leiden, The Netherlands
    Muscle Nerve 34:135-44. 2006
    ..In this study we provide an update of the mutational variability in the DMD gene, particularly focusing on genotype-phenotype correlations and mutations that appear to be exceptions to the reading-frame rule...
  10. pmc Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Mol Ther 17:548-53. 2009
    ..On the basis of only four parameters, we could correctly classify 79% of all AONs as effective or ineffective, suggesting these parameters can be used to more optimally design splice-modulating AONs...
  11. doi request reprint New insights in gene-derived therapy: the example of Duchenne muscular dystrophy
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Ann N Y Acad Sci 1214:199-212. 2010
    ..This review will explain the rationale and current state of affairs of these approaches and will then discuss how these gene-derived therapies might also be applicable to other diseases...
  12. pmc Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications
    Annemieke Aartsma-Rus
    DMD Genetic Therapy Group, Department of Human Genetics, Leiden University Medical Center, P O Box 9600, 2300 RC, Leiden, The Netherlands
    RNA 13:1609-24. 2007
    ..This knowledge allows us to optimize therapeutic exon skipping, but also opens up a range of other applications for the exon skipping approach...
  13. pmc Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    BMC Med Genet 8:43. 2007
    ..These mutations are in principle ideal targets for this approach since the specific skipping of duplicated exons would generate original, full-length transcripts...
  14. doi request reprint Exonic sequences provide better targets for antisense oligonucleotides than splice site sequences in the modulation of Duchenne muscular dystrophy splicing
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Oligonucleotides 20:69-77. 2010
    ..This suggests that exons may be better AON targets than introns per se, because of their higher GC content, which generally will result in improved AON binding...
  15. pmc Progress in therapeutic antisense applications for neuromuscular disorders
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 18:146-53. 2010
    ....
  16. doi request reprint Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon
    Melvin M Evers
    Department of Human Genetics, Leiden University Medical Center, The Netherlands
    Neurobiol Dis 58:49-56. 2013
    ..These results suggest that exon skipping may be a novel therapeutic approach to reduce polyglutamine-induced toxicity in spinocerebellar ataxia type 3. ..
  17. pmc Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy
    Dwi U Kemaladewi
    Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S4 P, PO Box 9600, Leiden, 2300RC, The Netherlands
    BMC Med Genomics 4:36. 2011
    ..In this study, we aim to knockdown myostatin by means of exon skipping, a technique which has been successfully applied to reframe the genetic defect of dystrophin gene in DMD patients...
  18. ncbi request reprint Exploring the frontiers of therapeutic exon skipping for Duchenne muscular dystrophy by double targeting within one or multiple exons
    Annemieke Aartsma-Rus
    DMD Genetic Therapy Group, Center for Human and Clinical Genetics, Leiden University Medical Center, RC Leiden, The Netherlands
    Mol Ther 14:401-7. 2006
    ..We aimed at inducing larger multiexon-skipping stretches, such as exons 17-51, exons 42-55, and exons 45-59. However, this appeared complicated and may be dependent on cotranscriptional splicing and the size of the flanking introns...
  19. ncbi request reprint Targeted exon skipping in transgenic hDMD mice: A model for direct preclinical screening of human-specific antisense oligonucleotides
    Mattie Bremmer-Bout
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Mol Ther 10:232-40. 2004
    ..These data highlight the high sequence specificity of this therapy and present the hDMD mouse as a unique model to optimize human-specific exon skipping in vivo...
  20. doi request reprint Accurate quantification of dystrophin mRNA and exon skipping levels in duchenne muscular dystrophy
    Pietro Spitali
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Lab Invest 90:1396-402. 2010
    ..The use of the same technique allows comparison between different groups working on exon skipping in the mdx mouse model...
  21. pmc Assessment of the feasibility of exon 45-55 multiexon skipping for Duchenne muscular dystrophy
    Laura Van Vliet
    DMD Genetic Therapy Group, Department of Human Genetics, Leiden University, Medical Center, Postzone S4 P, PO Box 9600, 2300RC, Leiden, The Netherlands
    BMC Med Genet 9:105. 2008
    ..The levels of intended multiexon skips are typically low and highly variable, and may be dependent on the order of intron removal. We hypothesized that the splicing order might favor the induction of multiexon 45-55 skipping...
  22. pmc Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Am J Hum Genet 74:83-92. 2004
    ..In fact, we here demonstrate its feasibility in myotubes from a patient with an exon 48-50 deletion. The application of multiexon skipping may provide a more uniform methodology for a larger group of patients with DMD...
  23. ncbi request reprint In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping
    Hans A Heemskerk
    DMD Genetic Therapy Group, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    J Gene Med 11:257-66. 2009
    ..In vivo studies are mainly performed using 2'-O-methyl phosphorothioate (2OMePS) or morpholino (PMO) AONs. These compounds were never directly compared...
  24. pmc Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase 2: inhibiting the receptor that is overactive in fibrodysplasia ossificans progressiva
    Songting Shi
    Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 8:e69096. 2013
    ..Our results therefore provide a potential therapeutic approach for the treatment of FOP disease by reducing the excessive ALK2 activity in FOP patients. ..
  25. ncbi request reprint Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Neuromuscul Disord 12:S71-7. 2002
    ..Accordingly, these antisense oligoribonucleotides would allow correction of over 50% of deletions and 22% of duplications reported in the Leiden DMD-mutation Database...
  26. doi request reprint A 3 months mild functional test regime does not affect disease parameters in young mdx mice
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Neuromuscul Disord 20:273-80. 2010
    ..We conclude that this test regime may be suitable for short-term functional evaluation of therapeutic approaches in the mdx mouse...
  27. ncbi request reprint Local dystrophin restoration with antisense oligonucleotide PRO051
    Judith C van Deutekom
    Department of Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    N Engl J Med 357:2677-86. 2007
    ..We explored the safety, adverse-event profile, and local dystrophin-restoring effect of a single, intramuscular dose of an antisense oligonucleotide, PRO051, in patients with this disease...
  28. ncbi request reprint Functional analysis of 114 exon-internal AONs for targeted DMD exon skipping: indication for steric hindrance of SR protein binding sites
    Annemieke Aartsma-Rus
    Leiden University Medical Center, Center for Human and Clinical Genetics, 2333 AL Leiden, The Netherlands
    Oligonucleotides 15:284-97. 2005
    ..Our results suggest that effective exon-internal AONs primarily act by blocking SR binding sites (which often correspond to open structures) and that ESEfinder may be used to refine AON design for DMD and other genes...
  29. pmc Preclinical PK and PD studies on 2'-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model
    Hans Heemskerk
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Mol Ther 18:1210-7. 2010
    ..c. administration, we selected this patient-convenient delivery method for future clinical study protocols...
  30. ncbi request reprint Gene expression profiling to monitor therapeutic and adverse effects of antisense therapies for Duchenne muscular dystrophy
    Peter A C 't Hoen
    Leiden University Medical Center, Center for Human and Clinical Genetics, Room S 04 003, Postbus 9600, 2300 RC Leiden, The Netherlands
    Pharmacogenomics 7:281-97. 2006
    ....
  31. doi request reprint Dose-dependent pharmacokinetic profiles of 2'-O-methyl phosphorothioate antisense oligonucleotidesin mdx mice
    Ingrid E C Verhaart
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Nucleic Acid Ther 23:228-37. 2013
    ..These studies underline the importance of balancing optimal AON efficacy and tolerable levels in non-target organs, which may be fine-tuned by further optimization of AON treatment regimens...
  32. doi request reprint Comparison of skeletal muscle pathology and motor function of dystrophin and utrophin deficient mouse strains
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Neuromuscul Disord 22:406-17. 2012
    ..This makes mdx/utrn +/- mice valuable for testing the benefit of potential therapies on muscle function parameters...
  33. doi request reprint Cell-type specific regulation of myostatin signaling
    Dwi U Kemaladewi
    Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S4 P, PO Box 9600, 2300RC, Leiden, The Netherlands
    FASEB J 26:1462-72. 2012
    ..Together, our results identify a molecular mechanism that explains the cell-type specific aspects of signaling by myostatin and other TGF-β family members...
  34. doi request reprint Development of antisense-mediated exon skipping as a treatment for duchenne muscular dystrophy
    Hans Heemskerk
    Duchenne Muscular Dystrophy Genetic Therapy Group, Department of Human Genetics, Leiden University, Medical Center, Leiden, The Netherlands
    Ann N Y Acad Sci 1175:71-9. 2009
    ..We propose that different chemistries should be further developed in parallel in order to hasten the transfer of the exon skipping therapy to the clinic...
  35. ncbi request reprint Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Hum Mol Genet 12:907-14. 2003
    ..These results document important progress towards a clinically applicable, small-molecule based therapy...
  36. ncbi request reprint Preventing formation of toxic N-terminal huntingtin fragments through antisense oligonucleotide-mediated protein modification
    Melvin M Evers
    1 Department of Human Genetics, Leiden University Medical Center, The Netherlands
    Nucleic Acid Ther 24:4-12. 2014
    ..Our proof of concept shows a completely novel approach to reduce mutant huntingtin toxicity not by reducing its expressing levels, but by modifying the huntingtin protein. ..
  37. pmc Prednisolone treatment does not interfere with 2'-O-methyl phosphorothioate antisense-mediated exon skipping in Duchenne muscular dystrophy
    Ingrid E C Verhaart
    Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Hum Gene Ther 23:262-73. 2012
    ..Overall these results show that the use of prednisone forms no barrier to participation in clinical trials with AONs...
  38. ncbi request reprint The therapeutic potential of antisense-mediated exon skipping
    Gert Jan van Ommen
    Leiden University Medical Center, Department of Human Genetics, Zone S4 P, PO Box 9600, 2300 RC Leiden, The Netherlands
    Curr Opin Mol Ther 10:140-9. 2008
    ..Antisense-mediated reading frame restoration is the most promising therapy for Duchenne muscular dystrophy. Data from a first clinical trial are encouraging and additional trials are ongoing or are expected to be initiated soon...
  39. ncbi request reprint Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 30:293-9. 2009
    ..Further research is needed to determine the functionality of different in-frame dystrophins and a number of hurdles has to be overcome before this approach can be applied clinically...
  40. doi request reprint Antisense-mediated exon skipping to correct IL-12Rbeta1 deficiency in T cells
    Esther van de Vosse
    Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
    Blood 113:4548-55. 2009
    ..We demonstrated that T cells can be highly efficiently transduced with AONs and are amenable to antisense-mediated exon skipping. Furthermore, we showed that exon skipping (partly) corrects the IL-12Rbeta1 deficiency in patients' cells...
  41. ncbi request reprint Peptide Conjugation of 2'-O-methyl Phosphorothioate Antisense Oligonucleotides Enhances Cardiac Uptake and Exon Skipping in mdx Mice
    Silvana M G Jirka
    1 Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Nucleic Acid Ther 24:25-36. 2014
    ..Based on these results, peptide conjugation represents an interesting strategy to enhance the therapeutic effect of exon skipping with 2'-O-methyl phosphorothioate AONs for Duchenne muscular dystrophy. ..
  42. doi request reprint Assessment of cardiac function in three mouse dystrophinopathies by magnetic resonance imaging
    Ingrid E C Verhaart
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Neuromuscul Disord 22:418-26. 2012
    ..Therefore magnetic resonance imaging is an adequate technique to determine heart function in dystrophinopathy mouse models and can be used to assess the effect of potential therapies...
  43. pmc Long-term Exon Skipping Studies With 2'-O-Methyl Phosphorothioate Antisense Oligonucleotides in Dystrophic Mouse Models
    Christa L Tanganyika-de Winter
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Mol Ther Nucleic Acids 1:e44. 2012
    ..Our results also indicate that long-term subcutaneous treatment in dystrophic mouse models with these AONs is safe and beneficial.Molecular Therapy-Nucleic Acids (2012) 1, e44; doi:10.1038/mtna.2012.38; published online 4 September 2012...
  44. doi request reprint Splice modulating therapies for human disease
    Pietro Spitali
    Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Cell 148:1085-8. 2012
    ..Effective approaches include restoring open reading frames, influencing alternative splicing, and inducing exon inclusion to generate beneficial proteins and remove deleterious ones...
  45. pmc BMP antagonists enhance myogenic differentiation and ameliorate the dystrophic phenotype in a DMD mouse model
    Songting Shi
    Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden, The Netherlands
    Neurobiol Dis 41:353-60. 2011
    ..In conclusion, our results suggest that repression of BMP signaling may constitute an attractive adjunctive therapy for DMD patients...
  46. doi request reprint Low dystrophin levels in heart can delay heart failure in mdx mice
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    J Mol Cell Cardiol 69:17-23. 2014
    ..Fibrosis was partly reduced from 9.8% in mdx to 5.4% in 10 month old mdx-Xist(Δhs) mice. These data suggest that mosaic expression of 4-15% dystrophin in the heart is sufficient to delay the onset and ameliorate cardiomyopathy in mice...
  47. doi request reprint Overview on applications of antisense-mediated exon skipping
    Willeke M C van Roon-Mom
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Methods Mol Biol 867:79-96. 2012
    ..For each application, examples are discussed and the current state of the art is described...
  48. pmc Targeting several CAG expansion diseases by a single antisense oligonucleotide
    Melvin M Evers
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 6:e24308. 2011
    ....
  49. pmc Inhibition of IL-1 Signaling by Antisense Oligonucleotide-mediated Exon Skipping of IL-1 Receptor Accessory Protein (IL-1RAcP)
    A Seda Yilmaz-Elis
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Mol Ther Nucleic Acids 2:e66. 2013
    ..Molecular Therapy - Nucleic Acids (2013) 2, e66; doi:10.1038/mtna.2012.58; published online 22 January 2013...
  50. doi request reprint Phage display screening without repetitious selection rounds
    Peter A C 't Hoen
    Center for Human and Clinical Genetics and Leiden Genome Technology Center, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Anal Biochem 421:622-31. 2012
    ..We conclude that next generation sequencing can significantly empower phage display screenings by accelerating the finding of specific binders and restraining the number of false positive hits...
  51. pmc Antisense-mediated isoform switching of steroid receptor coactivator-1 in the central nucleus of the amygdala of the mouse brain
    Ioannis Zalachoras
    Division of Medical Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University Leiden University Medical Center, Leiden, The Netherlands
    BMC Neurosci 14:5. 2013
    ..This nuclear receptor coregulator exists in two splice variants (SRC-1a and SRC-1e) which display differential distribution and opposing activities in the brain, and whose mRNAs differ in a single SRC-1e specific exon...
  52. ncbi request reprint Gene therapy for Duchenne muscular dystrophy
    Ingrid E C Verhaart
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Curr Opin Neurol 25:588-96. 2012
    ..Years of research have come to fruition during the past 18 months with publications on clinical trials for several gene therapy approaches for Duchenne muscular dystrophy. This review covers the present status of these approaches...
  53. doi request reprint Opportunities and challenges for the development of antisense treatment in neuromuscular disorders
    Maaike van Putten
    Leiden University Medical Center, Department of Human Genetics, The Netherlands
    Expert Opin Biol Ther 11:1025-37. 2011
    ..They are a frequent cause of disability and treatment options are often only symptomatic. Interestingly, for a number of neuromuscular disorders the application of antisense oligonucleotides has therapeutic potential...
  54. doi request reprint A novel feed-forward loop between ARIH2 E3-ligase and PABPN1 regulates aging-associated muscle degeneration
    Vered Raz
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands Electronic address
    Am J Pathol 184:1119-31. 2014
    ..We suggest that the expression of both genes is maintained by a feed-forward loop between mRNA stability regulated by PABPN1 and protein turnover regulated by ARIH2. ..
  55. doi request reprint Advances in therapeutic RNA-targeting
    Gert Jan B van Ommen
    Department of Human Genetics, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    N Biotechnol 30:299-301. 2013
    ..A final application, which is as yet under-explored but has major promise, is the functional in vivo study of protein isoforms by modulating their relative levels by AON-based skipping of alternative exons...