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Trends in Molecular Medicine
This journal offers authors two options (open access or subscription) to publish research

Feb 01, 2014

Volume 20Issue 2p63-128
Patient derived induced pluripotent stem cells (iPSCs) are now being used as a tool to study developmental diseases ex vivo. Differentiating iPSCs into neuronal cells can circumvent obstacles such as the inaccessibility of neuronal tissue and patient-specific variation. On pages 91–104 Prilutsky et al. review the recent progress using iPSCs to model autism spectrum disorders, and how phenotypic characterization may lack the reproducibility and stability to serve as an appropriate model. They suggest that by including gene expression profiling of iPSC-derived neurons, reproducible characterization may be achieved. Cover image from iStockphoto/dan4....
Patient derived induced pluripotent stem cells (iPSCs) are now being used as a tool to study developmental diseases ex vivo. Differentiating iPSCs into neuronal cells can circumvent obstacles such as the inaccessibility of neuronal tissue and patient-specific variation. On pages 91–104 Prilutsky et al. review the recent progress using iPSCs to model autism spectrum disorders, and how phenotypic characterization may lack the reproducibility and stability to serve as an appropriate model. They suggest that by including gene expression profiling of iPSC-derived neurons, reproducible characterization may be achieved. Cover image from iStockphoto/dan4.

Science & Society

  • Naming and framing in genomic testing

    • Eline M. Bunnik,
    • Maartje H.N. Schermer,
    • A. Cecile J.W. Janssens
    What's in a name? Terminology has the power to shape the ethical and regulatory debate surrounding commercially offered genomic testing. This article discusses the normative effects of naming and framing, and proposes that the medical frame, with its focus on the reduction of harm, should be used in the evaluation and regulation of predictive genomic testing.

Opinion

  • TDP-43-mediated neurodegeneration: towards a loss-of-function hypothesis?

    • Lies Vanden Broeck,
    • Patrick Callaerts,
    • Bart Dermaut
    TDP-43 is an evolutionarily conserved RNA/DNA-binding protein that plays a crucial role in ALS and FTD [1]. FTD is the second most common form of early-onset dementia after Alzheimer's disease (AD). The disorder is caused by a progressive loss of neurons from the frontal and temporal cortex leading to changes in speech, behavior, and personality, and later a broader decline of mental ability. ALS is a more rapidly progressive neurodegenerative disorder, in which motor neurons from the motor cortex and the anterior horn of the spinal cord are affected.

Reviews

  • Natural ligands and antibody-based fusion proteins: harnessing the immune system against cancer

    • Maulik Vyas,
    • Ulrike Koehl,
    • Michael Hallek,
    • Elke Pogge von Strandmann
    Monoclonal antibody (mAb) as cancer targeting therapy is regarded as one of the most successful and promising cancer immunotherapy approaches for several hematological and solid tumors [1]. Since US Food and Drug Administration (FDA) approval of the first therapeutic antibody, Rituximab in 1997, an additional 12 mAbs have been approved for the treatment of cancers [2], and a large number of therapeutic mAbs are currently under evaluation in clinical trials (see clinicalTrials.gov) [2]. Mechanistically, mAbs can employ one or more strategies to mediate antitumor actions [1,3].
  • The genetic relationship between handedness and neurodevelopmental disorders

    • William M. Brandler,
    • Silvia Paracchini
    Open Access
    Worldwide, more than 85% of individuals are right-handed [1,2]. This suggests there is an advantage to being right-handed, but also begs the question of why there are left-handers. Researchers have hypothesized that instead of being part of normal variation, there is a disadvantage to being left-handed. Consequently, left-handedness has been linked to all types of disorders, such as alcoholism [3], allergies and autoimmune disorders [4], autism [5], and these are only the disorders beginning with the letter ‘a’.
  • iPSC-derived neurons as a higher-throughput readout for autism: promises and pitfalls

    • Daria Prilutsky,
    • Nathan P. Palmer,
    • Niklas Smedemark-Margulies,
    • Thorsten M. Schlaeger,
    • David M. Margulies,
    • Isaac S. Kohane
    Autism spectrum disorders (ASDs; see Glossary) are a group of neurodevelopmental disorders characterized by deficits in social cognition, communication, and behavioral flexibility. There are no specific, approved pharmacological treatments for ASDs, and there are very few targets for drug development, although clinical trials with metabotropic glutamate receptor (mGluR) 5 antagonists, for example, AFQ056 (ClinicalTrials.gov, NCT01357239 ) to treat Fragile X syndrome (FXS) [1,2], and recombinant human insulin growth factor-1 (rhIGF-1) (ClinicalTrials.gov, NCT01777542 ) to treat Rett syndrome (RTT) [3] are underway.
  • α-1-Antitrypsin deficiency: clinical variability, assessment, and treatment

    • Robert A. Stockley,
    • Alice M. Turner
    The original observation of a missing α1 protein based on paper electrophoresis of blood samples resulted in the first description of the clinical features of α-1-antitrypsin-deficient (AATD) subjects [1]. The subsequent 20–25 years consolidated an association of basal panacinar emphysema (see Glossary) with AATD, the identification of neutrophil elastase (NE) as its cognate proteinase with the ability to cause emphysema in animal models [2], and the logical development of α-1-antitrypsin (AAT) augmentation by regular infusions to protect against and hence stabilise the ongoing NE-mediated lung damage.
  • The molecular and cellular pathology of α1-antitrypsin deficiency

    • Bibek Gooptu,
    • Jennifer A. Dickens,
    • David A. Lomas
    α1-Antitrypsin deficiency refers to a syndrome that may be characterised not only by a deficiency of circulating α1-antitrypsin but also by liver disease and/or emphysema. It was first identified, and an association with lung disease noted, by Laurell and Eriksson 50 years ago [1], and thus the history of its mechanistic elucidation and development of therapeutic strategies reflects that of molecular medicine (Box 1). The field has progressed from first defining the syndrome, using novel clinical investigation methods, through the application of genetic, biochemical, structural, cell biological, and animal models to stem cell approaches.
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